A high-reproducibility and high-precision exposure animal experiment system and method

Abstract

The application belongs to the technical field of toxicity test, and discloses a high-repetitive and high-precision exposure and poisoning animal experiment system and method. The exposure and poisoning animal experiment system comprises an animal exposure and poisoning experiment unit. The aerosol gas inlet sleeve, the poisoning exposure cabin, the isolation mouse cage, the horn-shaped upper guide cylinder and the cylindrical lower guide cylinder jointly form two mutually isolated poisoning exposure channels. Each channel independently inputs poisoning exposure mixed gas into a poisoning exposure chamber. The animal poisoning exposure experiment in the oral-nasal exposure mode or the whole-body exposure mode can be completed by using one set of experiment system. Through the synchronous improvement of the experiment system structure and the experiment method, the oral-nasal or whole-body exposure mode can be flexibly switched, and the micro-sample high-concentration exposure experiment of multiple poisoning exposure chambers can be simultaneously performed. The accuracy and repeatability of the animal poisoning exposure experiment are significantly improved. The application breaks through the limitations of the existing experiment system and method, and has a wide application prospect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of environmental protection, and particularly relates to a high-repetition and high-precision exposed animal experiment system and method. BACKGROUND

[0002] Currently, in animal exposure experiments, whole-body exposure and nose-only exposure are two common exposure methods, but they have significant differences in experimental equipment, methods and requirements, and each has advantages and disadvantages, and their application situations are different. Whole-body exposure and nose-only exposure must use their own equipment and methods to complete the whole-body exposure and nose-only exposure experiments, and obtain corresponding experimental results, which are two independent experimental methods and systems.

[0003] Among them, the whole-body exposure method and system expose the whole body of the animal (including the skin, respiratory tract, eyes, etc.) to the test substance (such as gas, aerosol or particulate matter), which is usually achieved through a sealed exposure chamber. The whole-body exposure method is simple to operate, but has many interference factors, the inhalation amount is difficult to control, and the data precision is relatively low. The whole-body exposure experiment is mainly used to study the influence of environmental pollutants on the overall health of animals. For example, in the evaluation of industrial pollution areas or chemical substance leakage sites, animals may be exposed to multiple harmful substances through multiple pathways such as respiration and skin contact. When the toxicity of a certain toxicant is not well understood, especially when the action pathway and mechanism are not well understood, whole-body exposure can observe the comprehensive effects of the toxicant on various systems of the animal, providing clues for subsequent research.

[0004] The nose-only or head-only exposure method and system expose only the nose and mouth of the animal to the test substance, and the rest of the body is isolated (such as through a head cover or a fixing device) to reduce the influence of non-respiratory exposure pathways. The inhalation amount of the nose-only exposure method is accurately controllable, but the equipment is complex, and the stress response of the animal may affect the experimental results. The nose-only exposure experiment is suitable for studying respiratory-related diseases or toxicological mechanisms, such as studying the damage of haze, industrial waste gas, etc. to the respiratory system. Nose-only exposure can more accurately simulate the process of humans inhaling harmful substances through the respiratory tract in similar environments, which helps to understand the pathophysiological changes and toxic action mechanisms of the respiratory tract. In particular, in the process of drug development, the safety and effectiveness of drugs administered through the respiratory tract are evaluated, including the development of inhalation anesthetics, asthma drugs, etc. Through nose-only exposure, the drug dose can be accurately controlled, and the effects of the drug on the respiratory tract and the whole body can be observed, providing a basis for the clinical application of the drug.

[0005] Therefore, each of the whole body exposure and the oral-nasal inhalation experiment has advantages and disadvantages, and the data accuracy depends on the experimental purpose and the characteristics of the test substance. The oral-nasal inhalation is superior in dose control and specificity, but the whole body exposure is superior in operational simplicity and ecological validity. The two in the prior art cannot be replaced or compatible with each other, and the experimental personnel need to comprehensively consider the experimental purpose, the nature of the test substance, the research goal, the animal species and other factors to select one of them.

[0006] The whole body exposure device is commonly used in chemical toxicity evaluation, biomedical research, environmental health research and the like, and the device usage rate is high. At present, the common whole body exposure device is mostly in the structure of a cuboid or a cube, and a small part is in the structure of a cylinder. The device generally adopts a dynamic circulation principle to continuously input the toxicant mixed with air into the cabin after the toxicant is mixed with air, and the exhaust gas is discharged after treatment. The toxicant dynamics simulation is performed to enable the exposed animals to absorb the toxicant through respiration and skin contact, simulate the real exposure route, and perform quantitative exposure. The inhalation dose (such as concentration x time x respiratory volume) is calculated through a mathematical model. During the experiment, the aerosol entering from the top needs to fill the entire internal structure, and then is discharged from the bottom or the side. For example, CN208805406U discloses an inhalation exposure device for toxicity test, which comprises an exposure device, an air inlet control device and an air outlet control device. The exposure device comprises a test cavity, a guide fan and a disturbance fan arranged in the test cavity, an animal placing plate for placing test animals is arranged in the test cavity, the animal placing plate has a gap with the bottom of the test cavity, a plurality of small holes are formed in the animal placing plate, a fixing frame is arranged between the guide fan and the disturbance fan in the test cavity, and a mosquito coil disc and / or an electric heater are placed on the fixing frame. Since the device is a whole body exposure animal experiment device, the data accuracy has great limitations. The dose estimation of whole body exposure is usually based on the concentration in the exposure cabin, but the actual inhalation volume of animals is affected by individual differences (such as respiratory volume and activity) and non-inhalation exposure, resulting in great data variability. Especially, in the research goal of clarifying respiratory toxicity, whole body exposure may introduce confounding factors due to skin absorption or licking behavior, which will significantly reduce the data specificity. CN1036267A discloses a self-controlled continuous test simulation exposure system, which adopts a dynamic gas distribution system and a tail gas treatment tank in addition to four exposure cabinets conforming to international standards. However, the actual inhalation volume is affected by factors such as animal activity and respiratory frequency, and the inhalation dose is difficult to accurately calculate, which also cannot replace the oral-nasal inhalation exposure experiment.

[0007] In summary, the above-mentioned whole body exposure device and experimental method cannot be compatible with and replace the oral-nasal inhalation exposure device and experimental method due to various technical limitations, has a single function, and has the following five limitations: first, the data precision and repeatability are relatively low, even if the whole body exposure device is optimized, the experimental data precision can be improved to a certain extent, but it still cannot completely reach the precision level of the oral-nasal inhalation method; second, the aerosol at the top fills the entire space, which causes uneven distribution of aerosol concentration, and the variation coefficient of the concentration and particle size distribution of the aerosol inhaled from different exposure areas is usually greater than 30%; third, the same volume of aerosol distributed in a larger space will cause a decrease in concentration, so it is difficult to achieve high-repeatability exposure experiments of trace test substances, especially whole body exposure experiments of some very valuable test substances; fourth, it is also difficult to obtain high-precision experimental data equivalent to oral-nasal exposure under high-repeatability conditions through synchronous control of the whole body exposure device and experimental method; and fifth, the experimental cost is high (equipment maintenance, consumables), a large number of experimental animals need to be disposed of after each experiment, and there is a greater ethical controversy. SUMMARY

[0008] In view of the deficiencies of the prior art, the purpose of the present application is to provide a high-repeatability and high-precision exposure animal experiment system and method, which improves and optimizes the exposure animal experiment system by setting two isolated exposure channels to enable the implementation of whole body exposure experiments or oral-nasal exposure experiments, achieving one machine with two functions; at the same time, the experimental method is improved, and the experimental animals are reasonably restricted or induced to maintain a better body position, and water and food are rewarded during the experiment, so that the head of the experimental animal can be concentrated in a small space with concentrated aerosol administration or uniform concentration distribution in the aerosol exposure chamber, which improves the repeatability of the inhaled aerosol concentration and particle size of the experimental animal, increases the aerosol concentration, reduces various interference factors, greatly improves the precision of the oral-nasal exposure inhalation amount and the whole body exposure experimental data, saves experimental reagents, and uses one set of exposure animal experiment system to perform two types of exposure experiments, which can be flexibly switched to obtain high-precision and high-repeatability data of oral-nasal exposure and whole body exposure experiments, thereby solving the above-mentioned problems.

[0009] The present application provides the following technical solutions to achieve the above-mentioned purposes:

[0010] A high-repeatability and high-precision exposure animal experiment system, comprising an animal exposure experiment unit, which comprises: an aerosol inlet sleeve, an exposure chamber, an isolation cage, a horn-shaped upper guide cylinder, and a cylindrical lower guide cylinder.

[0011] The exposure chamber is a closed chamber body with a whole profile in the shape of a shuttle and a hollow interior.

[0012] The aerosol air inlet sleeve is hollow inside, and the upper section is a mixing and dilution bin, and the lower section is arranged in the opening at the top of the exposure cabin;

[0013] The isolation mouse cage is a cylindrical ventilated flat cage with a whole annular shape, and is arranged at the middle section of the shuttle-shaped exposure cabin; the internal space of the isolation mouse cage is hollow near the center to form a through groove, and the remaining part is divided into a plurality of central-symmetric and independent exposure chambers.

[0014] The horn-shaped upper guide cylinder is a whole horn shape with an opening downward, and is arranged at the upper section of the shuttle-shaped exposure cabin 8; the upper section of the horn cylinder wall divides the internal space of the lower section of the aerosol air inlet sleeve into two mutually isolated gas passages; the outer side surface of the horn cylinder wall, the aerosol air inlet sleeve and the inner side surface of the exposure cabin jointly form a whole-body exposure diffusion zone, and the hollow inside of the horn cylinder wall forms a horn inner cylinder passage.

[0015] The cylindrical lower guide cylinder is a whole hollow cylinder, and is arranged in the through groove at the middle section of the isolation mouse cage; the hollow cylinder inner cylinder passage is in communication with the horn inner cylinder passage at the upper section, and is provided with a plurality of exposure chamber branch pipes at the bottom, which are directed to the front of each exposure chamber.

[0016] When the mixing and dilution bin is in communication with the horn inner cylinder passage, the cylindrical inner cylinder passage and the exposure chamber branch pipes, the exposure passage for inputting the exposure mixed gas into the independent exposure chamber, i.e. the oral-nasal exposure passage A, is formed, which is used for implementing the oral-nasal exposure animal experiment.

[0017] When the mixing and dilution bin is in communication with the whole-body exposure diffusion zone, the exposure passage for inputting the exposure mixed gas into the independent exposure chamber, i.e. the whole-body exposure passage B, is formed, which is used for implementing the whole-body exposure animal experiment.

[0018] The exposure and exposure animal experiment method with high repeatability and high precision is implemented by using the exposure and exposure animal experiment system with high repeatability and high precision; after the parts of the exposure and exposure animal experiment system with high repeatability and high precision are communicated, the aerosol and clean air are input into the mixing and dilution bin and mixed by the aerosol generator and the air compressor respectively, the two mutually isolated exposure passages, i.e. the oral-nasal exposure passage A and the whole-body exposure passage B, are switched by the exposure passage switching plug, the exposure mixed gas is independently input into each exposure chamber by one of the exposure passages, the animal exposure and exposure experiment in the oral-nasal exposure mode or the whole-body exposure mode is completed by using one set of experimental system, and the exposure and exposure animal experiment data with high repeatability and high precision is obtained.

[0019] Compared with the prior art, the exposure and exposure animal experiment system and method with high repeatability and high precision provided by the application has at least the following advantages and effects:

[0020] 1. This invention first improves and optimizes the animal exposure experiment system. In order to overcome the shortcomings of existing experimental systems and methods such as single function, two mutually isolated exposure channels are set up, which can carry out whole-body exposure experiments or oral-nasal exposure experiments at different times, realizing dual-purpose and flexible switching. In the small internal space of the exposure chamber (poison exposure chamber), it is easy to further restrict the position of the experimental animals, so that their heads are concentrated in the area with higher concentration of exposure gas. Higher concentration oral-nasal or whole-body exposure of rare or expensive samples can be carried out to improve the accuracy of exposure experiments and reduce the amount of reagents used.

[0021] 2. This invention further improves the experimental method, making the experimental method and experimental system compatible with each other, achieving dual-purpose functionality and flexible switching. By combining the physical passive restriction of the exposure chamber with induction, the experimental animals are encouraged to actively maintain a better body position. During the experiment, water and food rewards are used as inductions. The combination of passive and active measures ensures that the heads of the experimental animals are concentrated in a small space within the exposure chamber where aerosols are administered in a concentrated manner or where the concentration is evenly distributed. This improves the repeatability of aerosol concentration and particle size inhalation, increases aerosol concentration, reduces various interference factors, significantly improves the accuracy of data from oral and nasal exposure and whole-body exposure experiments, saves experimental reagents, and achieves high precision and high repeatability for both oral and nasal exposure and whole-body exposure experiments. One exposure animal experimental system can be used to conduct both types of exposure experiments and can be flexibly switched.

[0022] 3. Through simultaneous improvements in structure and experimental methods, this invention reduces the coefficient of variation of aerosol concentration and particle size distribution in laboratory animals in multiple isolated areas at different locations in current whole-body exposure experiments to less than 10%. It allows for the simultaneous conduct of high-concentration exposure experiments on trace samples using multiple independent oral-nasal or whole-body exposure methods. This design significantly improves the accuracy and repeatability of animal exposure experiments. The accuracy of oral-nasal inhalation exposure can replace conventional oral-nasal exposure equipment, and laboratory animals do not suffer the significant experimental stress caused by oral-nasal restraint in conventional oral-nasal inhalation experiments. The system and method of this invention can replace conventional oral-nasal inhalation exposure experiments and meet experimental accuracy requirements; simultaneously, it can greatly improve the data accuracy of whole-body exposure.

[0023] 4、The present application adopts the shuttle-shaped exposure cabin and two independent exposure passage structures, can effectively control the speed and direction of aerosol, reduce air resistance, avoid airflow interference and vortex effect, make the aerosol distribution in the exposure cabin have very good uniformity; can meet the long-term high-precision exposure of experimental animals, that is, under the condition that the animals grow continuously and their body weight and size increase, the size of the cage isolation area can be changed to individually isolate and limit the animal activity area, avoid the animal to move in a larger range, and the animal is in the position with more uniform aerosol concentration and particle size in the center of the exposure cabin;

[0024] 5、The exposure passage of the present application mainly releases exposure gas at the center position of the exposure cabin, cooperates with separately provided drinking water and feeding, provides the necessary premise for single long-time exposure (meets the survival needs of experimental animals), and enables the experimental animals to be in the position with more uniform aerosol concentration and particle size in the center of the exposure cabin for more time, thereby limiting the accuracy and repeatability of the animal exposure dose, greatly reducing the demand for hardware, experimental animals and consumables of the exposure experiment, reducing the experimental cost, and improving the animal welfare.

[0025] 6、The present application adopts high-precision mass flow controllers, single-chip microcomputers and software, can realize complete automatic control of pressure difference and concentration through PID control, has high control precision and fast response speed. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 It is a whole component structure schematic diagram of the exposure and animal experiment system of the embodiment of the present application;

[0027] Figure 2 It is a whole shape three-dimensional structure schematic diagram of the exposure cabin in the embodiment of the present application;

[0028] Figure 3 It is a three-dimensional assembly structure schematic diagram of the exposure cabin in the embodiment of the present application;

[0029] Figure 4 It is a front view structure schematic diagram of the exposure cabin in the embodiment of the present application;

[0030] Figure 5 It is a whole sectional structure schematic diagram of the exposure cabin in the embodiment of the present application; Figure 4

[0031] Figure 6 It is a three-dimensional structure schematic diagram of the inside of the exposure cabin in the embodiment of the present application;

[0032] Figure 7 It is a top view structure schematic diagram of the present application; Figure 6

[0033] Figure 8 ​​Fig. 1 is a schematic diagram of the perspective assembly structure of the present application; Figure 6 Fig. 2 is a schematic diagram of the front view structure of the present application;

[0034] Figure 9 Fig. 3 is a schematic diagram of the perspective assembly structure of the main structure of the present application; Figure 6 Fig. 4 is a schematic diagram of the front view structure of the present application;

[0035] Figure 10 Fig. 5 is a schematic diagram of the overall sectional structure of A-A in the present application; Figure 9 Fig. 6 is a schematic diagram of the overall sectional structure of B-B in the embodiment of the present application;

[0036] Figure 11 Fig. 7 is a schematic diagram of the perspective assembly structure of the partial structure of the present application; Figure 9 Fig. 8 is a schematic diagram of the perspective assembly structure of the partial structure in the embodiment of the present application;

[0037] Figure 12 Fig. 9 is a schematic diagram of the perspective assembly structure of the partial structure of the present application; Fig. 10 is a schematic diagram of the perspective assembly structure of the partial structure in the embodiment of the present application;

[0038] Figure 13 Fig. 11 is a schematic diagram of the front view structure of the embodiment of the present application; Figure 12 Fig. 12 is a schematic diagram of the sectional structure of A-A in the embodiment of the present application;

[0039] Figure 14 Fig. 13 is a schematic diagram of the front view structure of the embodiment of the present application; Figure 13 Fig. 14 is a schematic diagram of the sectional structure of A-A in the embodiment of the present application;

[0040] Figure 15 Fig. 15 is a schematic diagram of the sectional structure of A-A in the embodiment of the present application; Figure 14 Fig. 16 is a schematic diagram of the sectional structure of B-B in the embodiment of the present application;

[0041] Figure 16 Fig. 17 is a schematic diagram of the perspective external structure of the switching plug A of the exposure channel in the embodiment of the present application; Fig. 18 is a schematic diagram of the perspective external structure of the switching plug B of the exposure channel in the embodiment of the present application;

[0042] Figure 17 Fig. 19 is a schematic diagram of the control flow of the exposure experiment method in the embodiment of the present application.

[0043] Fig. 20 is a schematic diagram of the control flow of the exposure experiment method in the embodiment of the present application. Figure 18 Fig. 21 is a schematic diagram of the control flow of the exposure experiment method in the embodiment of the present application.

[0044] Fig. 22 is a schematic diagram of the control flow of the exposure experiment method in the embodiment of the present application.

[0045] 1, control computer; 2, single-chip microcomputer controller; 3, air compressor; 4, MFC; 5, clean air MFC; 6, aerosol generator;

[0046] 7, aerosol air inlet sleeve; 71, aerosol connecting pipe; 72, clean air connecting pipe; 73, plug slot; 74, mixing and dilution bin;

[0047] 8, exposure chamber; 81, upper cover; 811, sealing ring; 82, middle cabin coaming; 83, supporting plate; 84, lower cover;

[0048] 9, impactor; 10, exhaust treatment module; 11, particle size spectrometer; 12, exhaust MFC; 13, sampling MFC; 14, negative pressure vacuum pump; 15: differential pressure sensor, 16: particulate matter concentration sensor, 17: oxygen concentration sensor; 18, connecting line; 19, connecting pipeline;

[0049] 20, exposure channel switching plug;

[0050] 20a, exposure channel switching plug A; 20a1, plug A substrate; 20a1, plug A through hole;

[0051] 20b, exposure channel switching plug B; 20b1, plug B substrate; 20b2, plug B through hole;

[0052] 21, isolation mouse cage; 211, cage bottom plate; 212, cage cover plate; 2121, spliced cover sheet; 213, outer cage surrounding plate; 214, vertical partition plate; 215, through groove;

[0053] 22, horn-shaped upper guide cylinder; 221, horn cylinder wall; 222, cylindrical guide pipe; 223, guide pipe channel; 224, horn inner cylinder channel; 225, hollow horizontal support plate;

[0054] 23, cylindrical lower guide cylinder, 231, lower guide cylinder wall; 232, lower guide cylinder seat; 233, fin; 234, cylindrical inner cylinder channel; 235, exposed chamber branch pipe; 236, exposed chamber diffusion guide groove;

[0055] 24, drinking bottle; 241, bottle body; 242, bottle cap; 243, water supply pipe;

[0056] 25, oral-nasal exposure channel A;

[0057] 26, whole body exposure channel B; 261, whole body exposure diffusion zone;

[0058] 30, exposure chamber; 301, fan-shaped channel; 302, front and rear limit plug; 303, top lifting limit plate; 304, lifting bolt; 305, feed bin;

[0059] 35, aerosol exhaust pipeline interface; 36, exhaust sampling pipeline interface. DETAILED DESCRIPTION

[0060] In order to make the purpose, technical scheme and advantages of the present application more clear, the technical scheme of the present application will be further described in detail below in combination with the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application. In addition, the technical features involved in each embodiment of the present application described below can be combined with each other as long as they do not conflict with each other.

[0061] Embodiment 1

[0062] Referring to the accompanying drawings Figures 1-18 The embodiment provides an exposure and poisoning animal experiment system with high repeatability and high precision, which comprises an animal exposure and poisoning experiment unit, an operation support unit and an operation control unit, specific components and connection relationships of each unit are as shown in the drawings Figure 1 , which work together and the control principle is as shown in the drawings Figure 18 .

[0063] The animal exposure and poisoning experiment unit comprises an aerosol air inlet sleeve 7, a poisoning exposure cabin 8, an isolated mouse cage 21, a horn-shaped upper guide cylinder 22 and a cylindrical lower guide cylinder 23.

[0064] The operation support unit comprises an air compressor 3, an aerosol generator 6, a waste gas treatment module 10 and a negative pressure vacuum pump 14, which are communicated with each other through connecting pipelines 19 and finally communicated with the poisoning exposure cabin 8 respectively; the first air path of the air compressor 3 is connected to the aerosol connecting pipe 71 of the aerosol air inlet sleeve 7 through the aerosol generator 6 and the MFC 4 (aerosol generation air mass flow controller, referred to as generation MFC); the second air path is connected to the clean air connecting pipe 72 of the aerosol air inlet sleeve 7 through the clean air MFC 5 (clean air mass flow controller, referred to as clean air MFC); the waste gas treatment module 10 is communicated with the lower section of the poisoning exposure cabin 8 through the aerosol exhaust pipeline interface 35, and then connected with the first air path of the negative pressure vacuum pump 14 through the exhaust MFC 12 (exhaust air mass flow controller, referred to as exhaust MFC); the second air path of the negative pressure vacuum pump 14 is connected with the impactor 9 and the particle size spectrometer 11 through the sampling MFC 13 (sampling air mass flow controller, referred to as sampling MFC), and then communicated with the lower section of the poisoning exposure cabin 8 through the waste gas sampling pipeline interface 36.

[0065] The operation control unit comprises an operation control group and a concentration monitoring group which are connected with each other through connecting lines 18 or connecting pipelines 19; the operation control group is used for controlling the operation of each part of the exposure animal poisoning experiment unit and the operation support unit, and comprises a control computer 1, a single-chip microcomputer controller 2, a generation MFC 4, a clean air MFC 5, an impactor 9, a particle size spectrometer 11, an exhaust MFC 12 and a sampling MFC 13; the concentration monitoring group is used for real-time feedback data, and the input concentration is automatically adjusted after being calculated by the operation control group, so as to realize closed-loop control of the exposure animal poisoning experiment unit and the operation support unit, and comprises a differential pressure sensor 15, a particulate matter concentration sensor 16, an oxygen concentration sensor 17, the impactor 9 and the particle size spectrometer 11.

[0066] The specific connection mode is: the control computer 1 is connected with the single-chip microcomputer controller 2; the single-chip microcomputer controller 2 is connected with the MFC 4, the clean air MFC 5, the aerosol generator 6, the particle size spectrometer 11, the exhaust MFC 12 and the sampling MFC 13 respectively, and is connected with the differential pressure sensor 15, the particulate matter concentration sensor 16 and the oxygen concentration sensor 17; one end of the differential pressure sensor 15, the particulate matter concentration sensor 16 and the oxygen concentration sensor 17 is connected with the single-chip microcomputer controller 2, and the other end is connected with the aerosol air inlet sleeve 7, so as to correspondingly collect the pressure difference, the particulate matter concentration and the oxygen concentration of the mixed gas of the aerosol and the clean air in the mixed dilution bin 74; one end of the impact sampler 9 is connected with the exhaust gas sampling pipeline interface 36, and the other end is connected with the particle size spectrometer 11 and the sampling MFC 13; one end of the particle size spectrometer 11 is connected with the exhaust gas sampling pipeline interface 36, and the other end is connected with the sampling MFC 13; the MFC is the abbreviation of mass flow controller.

[0067] The exposure cabin 8 is a closed cabin body with a whole profile of a shuttle shape and a hollow inside, comprising: a covered hopper-shaped upper cover 81, a cylindrical middle cabin coaming 82, a funnel-shaped lower cover 84 and a supporting plate 83.

[0068] The whole profile of the covered hopper-shaped upper cover 81 is conical, and an opening is arranged at the center of the top thereof; the conical hollow part inside the covered hopper-shaped upper cover 81 is an upper section; the lower section of the aerosol air inlet sleeve 7 is embedded in the opening and extends into the inside of the covered hopper-shaped upper cover 81, and a sealing ring 811 is arranged at the gap between the aerosol air inlet sleeve 7 and the opening.

[0069] The middle cabin coaming 82 is a vertically arranged cylindrical coaming (made of transparent material), and the cylindrical hollow part inside the middle cabin coaming 82 is a middle section.

[0070] The whole profile of the funnel-shaped lower cover 84 is funnel-shaped, and the conical hollow part inside the funnel-shaped lower cover 84 is a lower section.

[0071] The lower end surface of the covered hopper-shaped upper cover 81 is buckled and sealed with the middle cabin coaming 82; the funnel-shaped lower cover 84 is an integral structure with the middle cabin coaming 82; a ring-shaped supporting plate 83 extending outward is arranged on the outer horizontal surface of the connecting part of the funnel-shaped lower cover 84 and the middle cabin coaming 82, which facilitates the movement of the whole exposure cabin 8.

[0072] The upper section, the middle section and the lower section are connected with each other to form a sealed structure inside the exposure cabin 8, and the isolation mouse cage 21, the horn-shaped upper guide cylinder 22 and the cylindrical lower guide cylinder 23 are arranged integrally in the sealed structure.

[0073] The aerosol inlet sleeve 7 is hollow inside, and the upper section is a mixing and dilution chamber 74, and the lower section is arranged in the opening at the top of the exposure chamber 8.

[0074] The aerosol inlet sleeve 7 is a hollow cylinder with a closed upper end and an open lower end, and a plug slot 73 is horizontally arranged on the side of the middle part of the hollow cylinder, and the upper part of the plug slot 73 is the upper section (mixing and dilution chamber 74), and the lower part of the plug slot 73 is the lower section arranged in the opening at the top of the exposure chamber 8.

[0075] The center of the upper end surface of the hollow cylinder of the aerosol inlet sleeve 7 is provided with an aerosol connecting pipe 71 for connecting the aerosol input pipeline;

[0076] A clean air connecting pipe 72 for connecting the clean air input pipeline is arranged on the side of the upper section of the hollow cylinder of the aerosol inlet sleeve 7;

[0077] The aerosol connecting pipe 71 and the clean air connecting pipe 72 converge above the plug slot 73 to form the mixing and dilution chamber 74.

[0078] The isolation mouse cage 21 is a cylindrical ventilated flat cage with a whole annular shape, and is arranged in the middle section of the shuttle-shaped exposure chamber 8; the inner space of the isolation mouse cage 21 is hollow near the center to form a through groove 215, and the remaining part is divided into a plurality of central symmetric and independent exposure chambers 30.

[0079] The horn-shaped upper guide cylinder 22 is a whole horn-shaped structure with an opening downward, and is arranged in the upper section of the shuttle-shaped exposure chamber 8; the upper section of the horn cylinder wall 221 divides the inner space of the lower section of the aerosol inlet sleeve 7 into two isolated gas passages: the outer side of the horn cylinder wall 221 and the inner side of the aerosol inlet sleeve 7 and the exposure chamber 8 together form a whole-body exposure diffusion zone 261, and the hollow inside of the horn cylinder wall 221 forms a horn inner cylinder passage 224.

[0080] The cylindrical lower guide cylinder 23 is a whole hollow cylinder, and is arranged in the through groove 215 in the middle section of the isolation mouse cage 21; the upper part of the hollow cylinder inner cylinder passage 234 is in communication with the horn inner cylinder passage 224, and the bottom part is provided with a plurality of exposure chamber branch pipes 235 leading to the front of each exposure chamber 30.

[0081] When the mixing and dilution chamber 74 is in communication with the horn inner cylinder passage 224, the cylindrical inner cylinder passage 234 and the exposure chamber branch pipe 235, an exposure passage for inputting the exposure mixed gas into the independent exposure chamber 30 is formed, that is, the oral-nasal exposure passage A 25, which is used for implementing the oral-nasal exposure animal experiment.

[0082] When the mixing dilution bin 74 is communicated with the whole body exposure diffusion zone 261, the exposure passage for inputting the exposure mixed gas into the independent exposure chamber 30, i.e. the whole body exposure passage B 26, is formed, which is used to implement the whole body exposure animal experiment.

[0083] The trumpet-shaped upper guide cylinder 22 comprises a columnar guide pipe 222, a trumpet cylinder wall 221, and a hollow horizontal support frame 225.

[0084] The upper section of the trumpet cylinder wall 221 is a hollow columnar guide pipe 222, which is arranged at the center position directly above the trumpet cylinder wall 221, and a guide pipe passage 223 is vertically arranged inside the columnar guide pipe 222 and communicated with a trumpet inner cylinder passage 224 inside the trumpet cylinder wall 221.

[0085] An annular hollow horizontal support frame 225 is further arranged on the lower end surface of the trumpet cylinder wall 221.

[0086] The trumpet-shaped trumpet cylinder wall 221 is arranged inside the covered hopper-shaped upper cover 81, and the hollow horizontal support frame 225 is arranged on the outer side surface of the bottom of the trumpet-shaped trumpet cylinder wall 221 and horizontally outwardly and deeply surrounds the trumpet-shaped trumpet cylinder wall 221.

[0087] The trumpet-shaped upper guide cylinder 22 is arranged directly above the cylindrical lower guide cylinder 23 through the annular hollow horizontal support frame 225, so that the trumpet inner cylinder passage 224 and the cylindrical inner cylinder passage 234 are aligned with each other and connected with the isolation mouse cage 21.

[0088] The columnar guide pipe 222 is inserted into the aerosol gas inlet sleeve 7, and the internal space of the lower section of the aerosol gas inlet sleeve 7 is divided into two mutually isolated gas passages: the outer side surface of the columnar guide pipe 222 and the inner side surface of the aerosol gas inlet sleeve 7 and the exposure cabin 8 together form the whole body exposure diffusion zone 261, which is part of the whole body exposure passage B 26; the hollow guide pipe passage 223 inside the columnar guide pipe 222 forms the upper section of the trumpet inner cylinder passage 224, which is communicated with the cylindrical inner cylinder passage 234 and the exposure chamber branch pipe 235 to form the oral-nasal exposure passage A 25.

[0089] After the external aerosol and clean air are mixed in the mixing dilution bin 74 of the upper section of the aerosol gas inlet sleeve 7, they are introduced into one of the two mutually isolated gas passages to correspondingly carry out the exposure experiment.

[0090] In order to facilitate the switching of the exposure passage, the animal exposure and exposure experiment unit of the embodiment further comprises an exposure passage switching insert 20.

[0091] The switching plug 20 of the exposure channel is a sheet-shaped substrate with a semicircle at one end, and two kinds of switching plugs with through-hole structures are arranged at different positions of the sheet-shaped substrate:

[0092] The switching plug A 20a of the exposure channel is provided with a center through-hole 20a2 at the center of the semicircle of the sheet-shaped substrate 20a1, and the part of the sheet-shaped substrate around the center through-hole 20a2 is closed;

[0093] The switching plug B 20b of the exposure channel is provided with a plum-blossom-shaped through-hole 20b2 around the center of the semicircle of the sheet-shaped substrate 20b1, and the center of the semicircle is closed;

[0094] The switching plug 20 of the exposure channel is plug-in arranged in the plug slot 73, and is used for switching the oral-nasal exposure channel A 25 and the whole-body exposure channel B 26:

[0095] When the switching plug A 20a of the exposure channel is inserted into the plug slot 73, the center through-hole 20a2 opens (conducts) the hollow conduit channel 223 inside the columnar conduit 222, so that the oral-nasal exposure channel A 25 is connected to the mixing and diluting bin 74 upward and to each exposure chamber 30 downward, and the whole-body exposure diffusion area 261 outside the columnar conduit 222 is closed, i.e. the entrance of the whole-body exposure channel B 26 is closed. The exposure mixed gas of aerosol and clean air mixed in the mixing and diluting bin 74 is input into each exposure chamber 30 through the oral-nasal exposure channel A 25 from the opening of the exposure chamber branch pipe 235, and is mainly inhaled by the experimental animals through the mouth and nose, so as to carry out the oral-nasal exposure experiment;

[0096] When the switching plug B 20b of the exposure channel is inserted into the plug slot 73, the plum-blossom-shaped through-hole 20b2 opens (conducts) the whole-body exposure diffusion area 261 outside the columnar conduit 222, so that the whole-body exposure channel B 26 is connected to each exposure chamber 30, and the conduit channel 223 inside the columnar conduit 222 is closed, i.e. the entrance of the oral-nasal exposure channel A 25 is closed. The exposure mixed gas of aerosol and clean air is input into each exposure chamber 30 through the whole-body exposure channel B 26 from the whole-body exposure diffusion area 261 outside the horn barrel wall 221 inside the exposure cabin 8, and is mainly absorbed by the experimental animals and partly adsorbed by the fur of the experimental animals, so as to carry out the whole-body exposure experiment.

[0097] In order to simplify the overall structure, the isolation mouse cage 21 of the embodiment is a semi-closed cage in the shape of a ring-shaped flat cylindrical cage, one side of which is open towards the center of the circle, and a through-hole 215 in the shape of a cylinder is formed in the hollow position around the center of the circle, which includes mutually engaged metal mesh plates, including a cage bottom plate 211, a cage cover plate 212, an outer cage surrounding plate 213, and a plurality of vertical partition plates 214; the openings in the metal mesh plates are a plurality of openings in the shape of a cylinder or a circle, and the openings in the shape of a cylinder are parallel to each other;

[0098] The cage bottom plate 211 is a ring-shaped metal mesh plate with a through-hole in the center (a through-hole in the center of the circle), which is arranged on the boss at the joint of the funnel-shaped lower cover 84 and the middle cabin surrounding plate 82;

[0099] The cage cover plate 212 is a metal mesh plate formed by mutually splicing a plurality of fan-shaped 2121 plate blocks, and the overall shape of the spliced plate block is a ring, each spliced cover plate 2121 covers the fan-shaped channel in the upper part of the dyeing and exposure chamber 30, and closes the fan-shaped channel of the dyeing and exposure chamber 30 from the upper part;

[0100] The outer cage surrounding plate 213 is a vertical plate arranged in a ring shape, with the head connected to the tail, and is arranged between the cage bottom plate 211 and the cage cover plate 212;

[0101] The vertical partition plate 214 is a vertical plate, and a plurality of vertical partition plates 214 are symmetrically arranged around the center, vertically arranged between the cage bottom plate 211, the cage cover plate 212, and the outer cage surrounding plate 213. The cylindrical lower guide cylinder 23 is arranged in the through-hole 215, and together divides the internal space of the isolation mouse cage 21 into a plurality of independent dyeing and exposure chambers 30. Each independent dyeing and exposure chamber 30 is a six-sided enclosed fan-shaped channel 301, and the fan-shaped channel 301 is narrow in front and wide at the back, and is used to place experimental animals;

[0102] In the experiment of the whole body exposure mode, the entire internal space of the fan-shaped channel 301 of each dyeing and exposure chamber 30 is used (larger), while in the experiment of the oral and nasal exposure mode, the front and rear limiting insertion plates 302 and the top lifting limiting plate 303 further reduce the front space of the fan-shaped channel 301, and forcibly limit the experimental animals in the narrow front space of the fan-shaped channel 301.

[0103] Specifically, in each independent dyeing and exposure chamber 30, a top lifting limiting plate 303 and a front and rear limiting insertion plate 302 are further arranged to limit the body position of the experimental animals; the top lifting limiting plate 303 is suspended on the cage cover plate 212 by a lifting bolt 304, and moves up and down during use, limiting the activity space of the experimental animals in the height direction of the fan-shaped channel 301;

[0104] The front and rear limiting plug-in plates 302 are vertically inserted in the middle of each fan-shaped channel 301 of the exposure chamber 30 (the insertion holes of the plug-in plates are inserted into the insertion holes of the plug-in strips arranged on the upper and lower sides of the fan-shaped channel 301), which divides the fan-shaped channel 301 of each exposure chamber 30 into two parts, and the experimental animals are placed in the front part, so that the experimental animals can only move their heads forward in the narrow space in the front part of the fan-shaped channel 301 (only the body position can be moved forward and backward, and cannot be turned around and jumped);

[0105] When the animal exposure experiment is performed, the top lifting limiting plate 303 is lowered, and the front and rear limiting plug-in plates 302 are moved forward, so that the experimental animals are limited in the fan-shaped channel 301 of the exposure chamber 30, and the experimental animals always keep their heads forward and cannot jump or turn around, so that the experimental animals are forced to passively approach the gas outlet of the exposure chamber branch pipe 235;

[0106] When the animal exposure experiment is performed, the top lifting limiting plate 303 is lowered, and the front and rear limiting plug-in plates 302 are moved forward, so that the experimental animals are limited in the fan-shaped channel 301 of the exposure chamber 30, and the experimental animals always keep their heads forward and cannot jump or turn around, so that the experimental animals are forced to passively approach the gas outlet of the exposure chamber branch pipe 235;

[0107] In order to accelerate the descending speed of the exposure mixed gas and reduce the high-concentration area during the whole-body exposure, a slope-shaped outer surface of the lower guide cylinder wall 231 is designed, and a guide and isolation fin 233 and an exposure chamber diffusion guide groove 236 are arranged on the outer surface corresponding to each exposure chamber 30, so as to improve the settling speed of the exposure mixed gas and gather the high-concentration exposure area near the center of the isolation cage 21 of each exposure chamber 30, and the specific structure is as follows:

[0108] The cylindrical lower guide cylinder 23 comprises a lower guide cylinder wall 231 and a lower guide cylinder base 232, a plurality of parallel fins 233 are vertically arranged on the outer side of the lower guide cylinder wall 231, and a cylindrical inner cylinder passage 234 is vertically arranged in the inner part of the lower guide cylinder wall 231, the lower end of the cylindrical inner cylinder passage 234 is closed by the lower guide cylinder base 232, and a plurality of exposure chamber branch pipes 235 are arranged from the inside to the outside at the position of the cylindrical inner cylinder passage 234 close to the lower guide cylinder base 232 and leading to the exposure chamber 30; the inclined cavity formed between the outer side of the lower guide cylinder wall 231 and the fin 233 is the exposure chamber diffusion guide groove 236, which communicates with each exposure chamber 30 from the outside of the lower guide cylinder wall 231;

[0109] The upper end surfaces of the lower guide cylinder wall 231 and the fin 233 are connected with the horn cylinder wall 221 and the hollow horizontal support frame 225, respectively, and the center of the lower guide cylinder wall 231 and the horn cylinder wall 221 are on a vertical line, and the cylindrical inner cylinder passage 234 of the cylindrical lower guide cylinder 23 communicates with the horn inner cylinder passage 224.

[0110] When the cylindrical downcomer 23 is integrally arranged in the through groove 215 of the isolated mouse cage 21, the upper and lower end faces of the downcomer wall 231 are flush with the cage bottom plate 211 and the cage cover plate 212, respectively, and the downcomer wall 231 and the fins 233 close the openings of the six faces of each exposure chamber 30 towards the center, so that the six faces of each exposure chamber 30 are closed (maintained breathable by the openings of the metal hole plate).

[0111] In order to further provide experimental accuracy and repeatability, a cavity (i.e. exposure chamber diffusion guide groove 236) is provided between the outer side of the downcomer wall 231 and the fins 233, which is in communication with the front end of each exposure chamber 30, and is close to the air outlet of the exposure chamber branch pipe 235, and is also used as a feed bin 305 to place the feed of experimental animals (placed in advance before the experiment starts).

[0112] The hollow horizontal support frame 225 is also provided with a plurality of water bottles 24 with bottle mouths facing downwards; the water bottles include a bottle body 241, a bottle cap 242 and a water supply pipe 243; the water supply pipe 243 extends downwards into the front part 301 of the fan-shaped passage of each exposure chamber 30, and the lower end is close to the air outlet of the exposure chamber branch pipe 235, for providing drinking water for experimental animals (drinking water is filled in advance before the experiment starts).

[0113] The feed bin 305 is provided with feed, and the water bottle 24 is provided with drinking water, which is used to attract experimental animals to actively approach the air outlet of the exposure chamber branch pipe 235 with their mouths and noses, so as to improve the total exposure inhalation dose and accuracy.

[0114] The high-repeatability and high-precision exposure and poisoning animal experiment method provided by the embodiment is implemented by using the high-repeatability and high-precision exposure and poisoning animal experiment system, as shown in Figure 1 After the parts of the high-repeatability and high-precision exposure and poisoning animal experiment system are sequentially communicated, the whole system can start to work. When working, refer to Figure 18 The system automatic control flow chart, in which the MFC reported flow is a dashed line and the single-chip microcomputer controlled MFC flow is a solid line.

[0115] The animal exposure experiment unit and the operation support unit are controlled by the operation control unit to work cooperatively. The main working process is as follows: according to the experimental design scheme, experimental animals are selected and put into each exposure chamber, then the operation control unit controls the aerosol generator 6 and the air compressor 3 to respectively input the aerosol and clean air into the mixing and diluting bin 74 and mix them, the mixed aerosol is obtained in the mixing and diluting bin, the two isolated oral-nose exposure channel A 25 and whole-body exposure channel B 26 are switched by the exposure channel switching plug 20, the mixed aerosol is independently input into each exposure chamber 30 through one of the two exposure channels, and the aerosol exposure experiment is carried out in the exposure cabin 8, so that the animal exposure experiment in the oral-nose exposure mode or the whole-body exposure mode is completed by using one set of experimental system, and high-reproducible and high-precision exposure experiment data of animals are obtained; the gas after completing the exposure experiment is discharged from the exposure cabin, and then waste gas sampling and waste gas treatment are carried out.

[0116] Referring to Figure 18 The single-chip microcomputer controller 12 is the core of the closed-loop adjustment of the experimental process. Generally, the flow rate of the aerosol generator is kept unchanged. If the concentration of the aerosol in the mixed aerosol collected by the particulate matter concentration sensor 16 is too high, the flow rate of the clean air is increased to reduce the concentration of the aerosol; on the contrary, if the concentration of the aerosol in the mixed aerosol collected by the particulate matter concentration sensor 16 is too low, the flow rate of the aerosol generator is increased or the flow rate of the clean air is reduced to increase the concentration of the aerosol, so as to maintain the stability of the aerosol concentration in the exposure cabin 8 during the experiment. Similarly, if the oxygen concentration in the mixed aerosol collected by the oxygen concentration sensor 17 is too high, the flow rate of the clean air is reduced, and vice versa, so as to maintain the stability of the oxygen concentration in the exposure cabin 8 during the experiment. If the pressure in the exposure cabin 8 collected by the pressure difference sensor 15 is too high, the exhaust flow rate is increased, and vice versa, so as to maintain the stability of the pressure in the exposure cabin 8 during the experiment. The control computer 1 is used for remotely controlling the single-chip microcomputer controller 2 to complete the complex closed-loop control process, and issuing instructions to the single-chip microcomputer controller 2, and the single-chip microcomputer controller 2 further controls the aerosol generator and each MFC to execute the instructions, so as to smoothly carry out the experiment.

[0117] Wherein, when the oral-nasal exposure experiment is implemented, the experimental animal is further limited in the front part of the fan-shaped channel 301 in the exposure chamber 30, the head is directed to the front part, the experimental animal cannot turn around and jump, and then the head of the experimental animal is provided with water and food reward, so that the animal stays in the small space near the outlet of the branch pipe 235 of the exposure chamber for a long time, so that the high-repetition exposure experiment of the animal is completed, and high-precision exposure experimental data close to the conventional oral-nasal exposure mode is obtained.

[0118] Wherein, when the whole-body exposure experiment is implemented, the experimental animal is further limited in the whole space of the fan-shaped channel 301 of the exposure chamber 30, and the experimental animal can move freely, and then the head of the experimental animal is provided with water and food reward, so that the animal moves in the space range close to the feed bin 305 and the aerosol concentration is uniform for a long time, so that the high-repetition exposure experiment of the animal is completed, and high-precision exposure experimental data higher than the conventional whole-body exposure mode is obtained.

[0119] The basic working principle of the embodiment of the present application is dynamic circulation, toxicology simulation (the animal absorbs the toxicant through respiration and skin contact, simulating the real exposure route) and quantitative exposure (the inhaled dose is calculated by a mathematical model, such as concentration x time x respiratory volume), and the specific connection of each part and the control mode of flow and concentration can all adopt conventional technologies, and thus will not be introduced in detail.

[0120] The high-repetition and high-precision exposure experiment method of the animal provided by the embodiment is implemented by using the high-repetition and high-precision exposure experiment system of the animal, one of the two mutually isolated oral-nasal exposure channels A 25 and the whole-body exposure channel B 26 is used to input the exposure gas into the exposure chamber 30, and the animal exposure experiment in the oral-nasal exposure mode or the whole-body exposure mode is completed by one set of experimental system, and high-repetition and high-precision exposure experiment data of the animal is obtained.

[0121] Embodiment 2

[0122] The high-repetition and high-precision exposure experiment system and method of the animal provided by the embodiment are based on the embodiment 1, and specifically provide an animal exposure experiment system and method in the oral-nasal exposure mode, and the high-repetition and high-precision exposure experiment of the animal in the lunar dust simulation particulate matter aerosol is implemented, the toxic effect of the lunar dust simulation particulate matter (simulating the lunar weathering layer composition) on the respiratory system, immune response and whole body organs (such as lung, liver and brain) of the mouse is explored through the oral-nasal exposure experiment, so as to reveal the potential fibrosis, oxidative stress and genotoxicity mechanism.

[0123] The high-repetition and high-precision exposure and poisoning animal experiment method and system used in this embodiment are basically the same as those in embodiment 1. When performing the oral and nasal exposure experiment, first, the body position of the experimental animal (mouse) needs to be strictly limited in the fan-shaped channel 301 in front of the exposure chamber 30 (passive control), the head is close to the outlet of the exposure chamber branch pipe 235, and the body can only move forward and backward, and cannot move left and right. Then the experiment is started. During the experiment, the experimental animal is provided with head drinking water, feeding and reward (active attraction), so that the animal's head is more in the small space near the outlet of the exposure chamber branch pipe 235 during the experimental time, so as to complete the high-repetition exposure and poisoning animal experiment, and obtain high-precision exposure experiment data close to or the same as the conventional oral and nasal inhalation method.

[0124] The animal exposure experiment system of embodiment 1 is used in this embodiment, and the experimental method further includes the following steps:

[0125] S1, experimental design

[0126] S1-1, experimental purpose

[0127] The toxic effects of lunar dust simulation particles (simulation of lunar regolith components) on the respiratory system, immune response and whole body organs (such as lungs, liver and brain) of mice through whole body exposure and poisoning device are evaluated, and the potential fibrosis, oxidative stress and genotoxicity mechanisms are revealed.

[0128] S1-2, experimental materials and main equipment

[0129] Experimental animals: SPF C57BL / 6 mice (half male and half female, 8 weeks old), randomly divided into groups:

[0130] Control group: clean air exposure (n=10)

[0131] Low dose group: lunar dust particles 100 mg / m³ (simulation of short-term lunar mission exposure, n=10)

[0132] High dose group: lunar dust particles 500 mg / m³ (simulation of long-term or high-concentration exposure, n=10)

[0133] Experimental substance:

[0134] Lunar dust simulation particles: refer to the standard formula of NASA JSC-1A / 1AV (containing plagioclase, pyroxene, olivine, ilmenite, etc.), particle size simulating real lunar dust (0.1-20 μm, irregular angular morphology).

[0135] Aerosol treatment: needs to be pretreated as completely dry particles.

[0136] The main equipment of the exposure and poisoning animal experiment system includes:

[0137] Aerosol generator (Venturi principle), lunar dust is directly sucked out by negative pressure and dispersed by compressed air to form aerosol during the experiment.

[0138] Real-time aerosol monitor (such as Grimm 1.109 aerosol monitor, which monitors the concentration of aerosol in real time);

[0139] Auxiliary equipment:

[0140] Air compressor and low-temperature dryer, used to simulate lunar low-humidity control (simulate lunar dry environment, humidity <10%);

[0141] Animal lung function detector (invasive lung function system);

[0142] Laser scanning confocal microscope (to observe the deposition of particles in lung tissue);

[0143] S2, preparation of experimental system

[0144] S2-1 First, according to Figure 1 As shown in FIG. 1, first, connect each part of the exposure and poisoning animal experimental system to each other, then insert the poisoning exposure channel switching plug A 20a into the plug slot 73, so that the oral and nasal poisoning exposure channel A 25 is in communication with each poisoning exposure chamber 30, and the inlet of the whole-body poisoning exposure channel B 26 is closed.

[0145] In this embodiment, the poisoning exposure cabin 8 is a transparent and wear-resistant shell with a whole profile of a hollow structure in the shape of a shuttle. The conical upper cover 81, the middle cabin coaming 82, and the lower cover 84 are designed with wear-resistant PC plastic or glass to prevent lunar dust simulation particles from being eroded. A sealing ring 811 is used to seal between the conical upper cover 2 and the cylindrical guide pipe 222 of the horn-shaped upper guide cylinder 22.

[0146] The isolation cage 21 is divided into a plurality of independent poisoning exposure chambers 30. Each poisoning exposure chamber 30 is surrounded by a cage bottom plate 211, a cage cover plate 212, an outer cage coaming 213, a vertical partition plate 214, and a lower guide cylinder wall 231. The cage cover plate 212 is an independent sector structure, and the cage cover plate 212 and the vertical partition plate 214 are detachable structures. The cage bottom plate 211 and the outer cage coaming 213 are provided with a plurality of slots (cylindrical openings). Each vertical partition plate 214 is inserted between the inner side of the outer cage coaming 213 and the cage bottom plate 211 (which is a whole circular structure) through the slot, and divides the space above the cage bottom plate 211. After covering the cage cover plate 212, a six-sided poisoning exposure chamber 30 is formed.

[0147] The cage cover plate 212 is formed by a plurality of fan-shaped spliced cover plates 2121 blocks spliced with each other, and the overall shape of the spliced cover plate 212 is a ring-shaped metal hole plate. Each spliced cover plate 2121 covers the fan-shaped channel 301 of the exposure chamber 30 from the top to seal the fan-shaped channel 301 of the exposure chamber 30;

[0148] According to the experimental design, the front and rear limiting plates 302 are vertically inserted into the middle part of the fan-shaped channel 301 of each exposure chamber 30, and the fan-shaped channel 301 of each exposure chamber 30 is divided into two parts. During the experiment, the experimental animals are placed in the front part, and the experimental animals are restricted to move forward only with their heads in the space in the front part of the fan-shaped channel 301. Then, the top limiting plate 303 is moved down, and the front and rear limiting plates 302 are moved forward. During the experiment, the specific positions of the lifting limiting plate 303 and the front and rear limiting plates 302 are adjusted according to the size of the experimental animals, so that the experimental animals are restricted in the front part of the fan-shaped channel 301 of the exposure chamber 30, and their heads are always forward, and they cannot jump or turn around, but only move their bodies slightly forward and backward. The experimental animals are forced to passively approach the gas outlet of the exposure chamber branch pipe 235 (semi-restraint) with their mouths and noses;

[0149] S2-2 connects the operation control unit and the operation support unit, and performs operation control and operation support respectively. According to the experimental design, the concentration and flow of the exposure mixed gas are controlled. The real-time detection feedback operation data of each sensor are calculated by the control computer 1 and the single-chip microcomputer controller 2 of the operation control automatic unit, and then the input concentration and pressure are adjusted for closed-loop control. At the same time, the environment is controlled during the experiment to maintain constant temperature and humidity, so as to reduce the stress of the animals.

[0150] S2-3 preparation of experimental animals and experimental substances

[0151] Experimental animals and experimental substances are prepared respectively, and lunar dust simulation particulate matter aerosol is prepared.

[0152] Particulate matter activation: lunar dust simulation particulate matter is prepared, and then the lunar dust simulation particulate matter is baked at high temperature (200°C, 2 hours) to remove organic matter, simulating the non-adsorption characteristics in the vacuum environment of the moon.

[0153] Aerosol preparation: the aerosol generator (Venturi suction and spray generator) is driven by dry air to disperse the particles, and the mass concentration is controlled to be 100-500 mg / m³, and the particle size peak value is 1-3 μm (simulating the inhalable range).

[0154] S3, implementation of oral and nasal exposure animal experiment

[0155] The exposure scheme includes:

[0156] Exposure cycle: 4 hours per day, 4 weeks continuously (simulating long-term lunar base mission);

[0157] Chamber environment: temperature 25±1 °C, humidity <10%, CO2 concentration maintained at 0.5% (simulating spacesuit leakage risk scenario).

[0158] Dynamic exposure control: chamber particle concentration was monitored every 15 minutes, and the airflow velocity was automatically calibrated when the deviation was >10%;

[0159] Aerosol leakage risk control: Chamber 8 was slightly positive pressure to allow more sufficient exposure of animals to precious samples, but there was a risk of leakage. A HEPA+ULPA three-stage filter was connected in series at the outlet of Chamber 8 to prevent simulated lunar dust leakage. Aerosol generator 6 and Chamber 8 needed to be placed in a biological safety cabinet for experiments, and the experimenters wore N95 masks.

[0160] Animal welfare (ethics) guarantee: experimental animals were in a semi-restrained state, and free drinking water and feed were provided during exposure to ensure adequate animal welfare.

[0161] S3-1 Set exposure parameters such as aerosol concentration, Chamber 8 pressure (slightly positive pressure), and minimum ventilation in the control software of the running control unit, and set environmental control parameters, etc.

[0162] S3-2 Start the experiment under the control of environmental control parameters: after grouping, place the mice in each exposure chamber 30 of the isolated cages 21 in Chamber 8, ensure that each mouse is isolated in the exposure chamber 30, maintain a constant temperature (22±2°C) and humidity (50±10%), add sufficient food to the feed bin 305, and add enough clean drinking water to the drinking bottle 24 to ensure the mice's 6-hour feeding and drinking needs; each mouse is in a semi-restrained position due to the narrow space of the fan-shaped passage 301 of each exposure chamber 30 in the isolated cage 21, and cannot turn around or run.

[0163] S3-3 According to the set exposure parameters, the exposure aerosol gas (mixed with clean air to adjust its concentration) is introduced into the exposure cabin 8 by the aerosol generator 6, each concentration monitoring sensor feeds back the data in the exposure cabin 8 in real time, and sends it to the operation control unit, automatically adjusts the concentration of the input aerosol and oxygen, and carries out closed-loop control; at the same time, during the exposure experiment, the mice are provided with free drinking water and feed, so that the heads of the mice are all in the position close to the center of the exposure cabin 8, the animals are induced to actively approach the gas outlet (high-concentration and uniform particle size distribution area) of the exposure chamber branch pipe 235, so as to improve the total exposure inhalation dose and accuracy; and the breathing frequency of the mice is stable and close to the normal physiological value; until the exposure time is reached, the introduction of the exposure aerosol is stopped; during the exposure experiment, the aerosol generator 6 processes the gas in the exposure cabin 8 after the exposure experiment according to the set flow, and then sucks it out to the outside of the exposure cabin 8 under negative pressure, so as to maintain the exposure aerosol concentration and pressure in the exposure cabin 8;

[0164] S3-4 After the exposure time (4 hours per day, continuously for 4 weeks) is reached, the experimental animals mice are taken out, samples are collected, and then detection is carried out;

[0165] S4, experimental data analysis

[0166] The physiological data, activity data of the experimental animals collected during the experiment, and the data obtained from the animal samples are analyzed after being summarized, and the toxicity effect data of the respiratory system, immune response and whole body organs of the experimental animals in the whole body exposure experiment are obtained, including the following contents:

[0167] S4-1 Respiratory system evaluation:

[0168] Lung function: detection of airway resistance (Raw), lung compliance (Cchord).

[0169] Bronchoalveolar lavage fluid (BALF): analysis of total protein content, lactate dehydrogenase (LDH, lung injury marker), inflammatory cell classification count.

[0170] Lung tissue pathology: Masson trichrome staining (collagen deposition), transmission electron microscopy (observation of lunar dust particles penetrating alveolar barrier).

[0171] S4-2 Oral toxicity analysis:

[0172] Oxidative stress: detection of lung and liver tissue MDA, SOD, GSH-Px;

[0173] Systemic inflammation: serum IL-1β, IL-6, TNF-α (Luminex multi-factor detection);

[0174] Genotoxicity: Comet assay of peripheral blood lymphocytes (DNA damage degree);

[0175] Brain tissue impact: Iba-1 immunohistochemistry of microglial activation marker;

[0176] S4-3 Analysis of dust clearance kinetics in 3 months:

[0177] The content of silicon (Si), iron (Fe), and titanium (Ti) in the lung and spleen was quantified using inductively coupled plasma mass spectrometry (ICP-MS) to evaluate the systemic migration of lunar dust simulation particles.

[0178] S4-4 Experimental analysis results

[0179] Interstitial fibrosis (collagen area increased by more than 30%) was observed in the lung tissue of high-dose group mice, and the activity of LDH in BALF was significantly increased.

[0180] The increase in serum IL-6 levels suggests a systemic inflammatory response.

[0181] Brain microglial activation may be related to the penetration of lunar dust nanoparticles through the blood-brain barrier.

[0182] Through actual experiments, it is found that the technical solutions and experimental results provided in the embodiment also include the following unique aspects:

[0183] (1) Lunar dust specific exposure simulation:

[0184] The particle aerosol generator 6 using the Venturi effect principle does not need to compress the lunar dust particles into a powder cake and then further shave and blow them apart. Instead, it only needs to place the treated lunar dust into the disc of the aerosol generator 6 and directly form an aerosol through the Venturi suction and spraying method. This can very well reproduce the electrostatic adsorption characteristics of lunar surface particles.

[0185] (2) Aerosol uniformity: The space of the exposure chamber 8 and the isolation cage 21 is designed reasonably to optimize the particle size distribution and concentration uniformity of the aerosol inside, such as the use of a shuttle-shaped exposure chamber structure to reduce turbulence during aerosol settling. The use of an open and closed upper cover 81 to load and unload experimental animals can minimize the height of the exposure chamber 8 and reduce the internal volume occupied. The central position of the isolation cage 21 in the exposure chamber 8 is a whole trumpet-shaped structure, which is beneficial to the uniform and rapid diffusion of the aerosol input from the top to each exposure chamber 30.

[0186] (3) Dose accuracy: The actual inhaled dose was calculated according to the exposure time and the breathing rate (about 150 times per minute for mice). The animals were subjected to the limitations of the isolation cage 21 and could not move freely. All mice were almost in the same position (the center position in the exposure chamber 8 where the concentration and particle size distribution were the most uniform), and the mice were in a semi-restrained state. In addition, food and water were provided, and the breathing rate of the animals was more stable and close to the normal physiological value during the entire experiment. Therefore, the inhaled dose calculated was more accurate, and the repeatability was very high, which was similar to the concentration deviation (less than 10%) through the traditional oral and nasal inhalation exposure method.

[0187] (4) Low sample high concentration exposure: Due to the difficulty in obtaining lunar dust simulant, it is necessary to achieve high concentration exposure experiments with minimal consumption. Therefore, it is desirable that the volume of the animal exposure chamber 8 (especially each exposure chamber 30) is smaller to reduce the collision probability of particles inside the particle aerosol generator 6, so as to achieve low-dose high-concentration experiments. The system and method provided in this embodiment can fully meet these requirements by combining the exposure chamber 8 and the experimental method, and provide a feasible scheme for high-precision exposure experiments of various precious materials.

[0188] (5) Multi-organ toxicity joint detection:

[0189] The local lung injury can be combined with systemic inflammation and neurotoxicity to comprehensively evaluate the health risks of lunar dust.

[0190] (6) Dose equivalence design:

[0191] The equivalent dose for humans can be calculated according to the minute ventilation of mice (MV = 0.025 L / min).

[0192] Embodiment 3

[0193] The high-repeatability and high-precision exposure and animal experiment system and method provided in this embodiment are basically the same as those in Embodiment 1 and Embodiment 2, except that an animal exposure experiment system and method for whole-body exposure is provided, specifically an experimental system and method for studying the toxicity of DEP dry powder particles to the respiratory system of mice.

[0194] The exposure of the animal experiment system used in this embodiment is the same as that in Embodiments 1 and 2, and the difference is that, when the whole-body exposure animal experiment is performed, the experimental animal is limited in a larger space of the exposure chamber 30 (not bound), and the front and rear limiting plates 302 and the top lifting limiting plate 303 are not needed, and the experimental animal mouse can freely move in the fan-shaped channel 301, including turning around, jumping, etc., and then the mouse is provided with head drinking water and feeding reward, so that the mouse moves in a smaller space range close to the feed bin 305, the aerosol concentration is uniformly distributed, and the center position of the isolation cage 21, to complete the high-repetitive whole-body exposure animal experiment, and obtain high-precision exposure experimental data higher than that of the conventional whole-body exposure.

[0195] The whole-body exposure animal experiment system and method provided in this embodiment specifically includes the following contents.

[0196] S1, experimental design

[0197] S1-1, purpose of the experiment

[0198] The influence of DEP (Diesel Exhaust Particles) on the respiratory system of mice through the whole-body exposure device was studied, and the toxicity mechanism (such as inflammatory response, oxidative stress, histopathological changes) was evaluated to understand the influence of motor vehicle exhaust emissions on human health.

[0199] S1-2, experimental materials and main equipment

[0200] Experimental animals: SPF male C57BL / 6 mice (8 weeks old, weighing 20-25 g), randomly divided into control group and exposure group (n=10 in each group).

[0201] Experimental substance: DEP dry powder particles, which need to be pretreated as completely dry particles.

[0202] Main equipment of the whole-body exposure system:

[0203] Aerosol generator 6 (Venturi effect principle), exposure chamber 8, real-time aerosol concentration monitor (such as laser particle counter), waste gas treatment, etc.

[0204] Auxiliary equipment: clean air compressor, biological safety cabinet.

[0205] S2, preparation of the experimental system

[0206] S2-1, set up the whole-body exposure animal experiment unit, connect the aerosol introduction device, the exposure chamber device, and the aerosol export device through the ventilation pipeline;

[0207] Insert the exposure switching plug B 20b into the plug slot 73, and the plug's star-shaped through hole opens the whole-body exposure diffusion zone 261 outside the cylindrical duct 222, so that the whole-body exposure channel B 26 is in communication with each exposure chamber 30, and the exposure mixture of aerosol and clean air is evenly diffused from the hollow part outside the horn barrel wall 221 and the lower guide cylinder wall 231, especially along the arc slope of the horn barrel wall 221, and is quickly input into the lower part of each exposure chamber 30 to carry out the whole-body exposure experiment; at the same time, the duct channel 223 inside the cylindrical duct 222 is closed, i.e. the entrance of the oral-nasal exposure channel A 25 is closed;

[0208] S2-2 Set the operating parameters of the operation control unit to control the operation of the aerosol generator 6, the exposure chamber 8, and the waste gas guide in the whole-body exposure animal experiment unit by the operation control unit;

[0209] The sensors feed back the concentration monitoring data in real time, and the operation control unit automatically adjusts the input concentration for closed-loop control.

[0210] During the experiment, the temperature and humidity are kept constant to reduce the stress of the animals.

[0211] S2-3 Prepare experimental animals and experimental substances

[0212] Prepare experimental animals and experimental substances respectively, and prepare aerosol: use a dry powder aerosol generator to disperse DEP particles into stable aerosol, which is driven by compressed air and introduced into the mixing and dilution bin 74 at the top of the exposure chamber 8.

[0213] The operation control unit automatically adjusts the mass concentration of particles in the exposure chamber 8 to, for example, 100-500 μg / m³ by PID control, and the system automatically starts the experiment after the concentration reaches a stable value; the particle size distribution is monitored in real time during the experiment, including controlling the median particle size of PM2.5 to ≤2.5 μm, etc.

[0214] S3, Whole-body exposure animal experiment

[0215] S3-1 Set the exposure parameters in the control software of the operation control unit, such as exposure aerosol concentration, experimental chamber pressure (slightly positive pressure), minimum ventilation volume, etc.; at the same time, set the environmental control parameters, such as temperature, humidity, and oxygen concentration, etc.

[0216] S3-2 Under the control of environmental control parameters, the mice are grouped and placed in the isolation cages 21 in the exposure chamber 8, specifically in each exposure chamber 30, to ensure that each mouse is isolated; the exposure chamber 8 is maintained at a constant temperature (22±2°C) and humidity (50±10%), sufficient food is pre-added to the feed bin 305, and sufficient clean drinking water is added to the drinking bottle 24 to ensure the mice's 6-hour food and water needs; each mouse is in a non-restrained state and cannot move at will due to the isolation cage.

[0217] Exposure parameters: 6 hours per day for 5 consecutive days (simulating subacute exposure), and the control group is exposed to filtered clean air;

[0218] Real-time monitoring of the concentration of particulate matter in the chamber (such as Grimm 1.109 aerosol monitor) to ensure dose consistency;

[0219] S3-3 According to the set exposure parameters, the aerosol generator introduces exposure aerosol into the exposure chamber 8, the particulate matter concentration sensor 16 feeds back the data in the exposure chamber 8 in real time and sends it to the operation control unit, which automatically adjusts the input concentration, etc., for closed-loop control; at the same time, during the exposure experiment, the mice are provided with free drinking water through the water supply pipe 243 of the drinking bottle 24 and food through the feed bin 305, so that the mice's head is in a position close to the center of the exposure chamber 8 with uniform concentration and particle size distribution for a long time, and the mice's breathing rate is stable and close to the normal physiological value; until the exposure time is reached, stop introducing exposure aerosol; during the exposure experiment, the gas in the exposure chamber 8 that has completed exposure is pumped out to the outside of the exposure chamber 8 at a set flow rate for treatment, and the concentration of exposure aerosol in the exposure chamber 8 is maintained;

[0220] Control the uniformity of aerosol: through the combined optimization design of the exposure chamber 8, the isolation cage 21, and the horn-shaped upper guide cylinder 22 and the cylindrical lower guide cylinder 23, the particle size distribution and concentration uniformity of the aerosol in each exposure chamber 30 are significantly enhanced; the overall exposure chamber 8 adopts a shuttle-shaped exposure chamber structure to reduce turbulence during aerosol settling; the horn-shaped upper guide cylinder 22 is arranged at the central position of the isolation cage 21 in the exposure chamber 8 to form each exposure chamber 30, and the horn-shaped upper guide cylinder 22 at the upper part can quickly introduce the aerosol to the front part (close to the center) of each exposure chamber 30, and then uniformly diffuse from front to back, with high aerosol uniformity and greatly improved aerosol utilization rate.

[0221] Accuracy of exposure dose: The actual inhaled dose was calculated according to the exposure time and the breathing frequency (about 150 times per minute for mice), and the experimental animals were subjected to the physical limitations of the individual exposure chambers 30 of the isolated cages 21 during the experiment, and could not move at will, all the mice were almost in the same position (the position was the front of the exposure chamber 30 with the most uniform concentration and particle size distribution in the exposure cabin 8, and the feeding and watering position), and the mice were in a non-restrained state, and the breathing frequency of the animals was more stable and close to the normal physiological value during the whole experiment, so that the inhaled dose calculated was more accurate, and the repeatability was very high, and the concentration deviation of the traditional whole body exposure method was greatly reduced (less than 10%).

[0222] Guarantee animal welfare: The animals are in a non-restrained state experiment, and free drinking water and feed are provided during exposure, and the animal welfare can be fully guaranteed.

[0223] S3-4 After reaching the exposure time (6 hours per day, continuously for 5 days), the experimental animals were taken out and prepared as samples for testing;

[0224] Some matters needing attention during the experiment of the exposed animals:

[0225] Risk of aerosol leakage: The exposure cabin 8 is slightly positive pressure, which can more fully expose the animals to precious samples, but there is a risk of leakage, so the aerosol generator and the exposure cabin 8 need to be placed in a biological safety cabinet for experiment, and the experimenters wear N95 masks.

[0226] Reduce particle collision loss: During the experiment, the connecting pipeline from the aerosol generator to the exposure cabin 8 should be as short as possible (not more than 1 meter), and fans should not be used for dilution and mixing in the exposure cabin 8 to cause collision, and the shuttle airflow design is used to reduce the turbulence during the settling process of the particles in the cabin.

[0227] Data comparability: The control group and the exposure group need to be raised in the same environment at the same time to exclude environmental interference.

[0228] S4, analysis of experimental data

[0229] The physiological data, activity data of the experimental animals collected during the experiment, and the data obtained from the animal samples are analyzed after being summarized, and the toxicity effect data of the respiratory system, immune response and whole body organs of the experimental animals in the whole body exposure experiment are obtained.

[0230] S4-1 Respiratory function test: After exposure, the lung function of the mice (such as airway resistance and tidal volume) is detected by whole body plethysmography (WBP).

[0231] Bronchoalveolar lavage fluid (BALF) analysis: detection of inflammatory cell count (neutrophils, macrophages), inflammatory factors (IL-6, TNF-alpha).

[0232] Histopathological analysis: take lung tissue for HE staining, observe alveolar structure destruction, inflammatory infiltration.

[0233] Oxidative stress index analysis: detection of lung tissue SOD, MDA, GSH levels.

[0234] Analysis results obtained in S4-2 experiment

[0235] The lung function of the exposed group of mice decreased, and the inflammatory cells and factors in the BALF increased significantly.

[0236] Lung tissue pathology showed alveolar wall thickening and inflammatory cell infiltration.

[0237] Oxidative stress markers (such as MDA) increased, and the activity of antioxidant enzymes (such as SOD) decreased.

[0238] The technical solutions and effects provided by the embodiments are unique and include the following parts:

[0239] The embodiments improve the system and method, focusing on overcoming the shortcomings of the existing whole-body exposure device structure and experimental method. First, the aerosol at the top fills the entire space, causing uneven distribution of aerosol concentration. Second, the same volume of aerosol distributed in a larger space will cause a decrease in concentration, so high-reproducible exposure experiments can be realized, especially for some valuable test substances that require whole-body exposure experiments. At the same time, high-precision experimental data under high-reproducible conditions can also be obtained.

[0240] The experimental system and experimental method provided by the above embodiments of the present application are combined with each other, which can reduce the coefficient of variation of the concentration and particle size distribution of inhaled aerosol between animals at different positions in the two exposure mode experiments to within 10%, and can carry out high-concentration exposure experiments of trace samples in oral-nasal or whole-body exposure mode, thereby significantly improving the precision and reproducibility of animal exposure experiments. The oral-nasal mode can replace the conventional oral-nasal inhalation exposure experiment, and the animals do not need to suffer from the great experimental stress caused by restraint in conventional oral-nasal inhalation experiments. Compared with conventional experimental systems and methods, the above embodiments of the present application have the advantages of high system utilization rate, low cost (equipment maintenance, consumables), less experimental substances required, suitable for carrying out trace substance exposure experiments, good uniformity of exposure substance concentration and particle size distribution, high automation degree, ability to be placed in a biological safety cabinet for high-toxicity substance experiments, guaranteed experimental animal welfare, no experimental ethics controversy, etc., and have a broad application prospect.

[0241] It should be noted that other different schemes obtained by making specific selection within the scope of the structure, step, process parameter and condition described in the present application can achieve the technical effects described in the present application, and therefore the present application will not list them one by one.

[0242] The above description is only the preferred embodiment of the present application, and does not limit the present application in any form. Any person skilled in the art can make many possible changes and modifications to the technical solutions of the present application, or modify them into equivalent embodiments with equivalent changes, without departing from the scope of the technical solutions of the present application, and all of them are within the protection scope of the present application.

Claims

1. A high-reproducibility and high-precision exposure animal experiment system, comprising an animal exposure experiment unit, the experiment unit comprising: an exposure cabin, which is a closed cabin with a shuttle shape and a hollow interior; an aerosol inlet sleeve, which is hollow and has a mixing and dilution chamber at an upper section and is arranged in an opening at a top of the exposure cabin; an isolated mouse cage, which is a cylindrical gas-permeable flat cage with a ring shape as a whole and is arranged in a middle section of the shuttle-shaped exposure cabin; an interior space of the cage, which is hollow near a center and forms a through groove, and the rest of the space is divided into a plurality of center-symmetrical and independent exposure chambers; a horn-shaped upper guide cylinder, which is horn-shaped with an opening downward as a whole and is arranged in an upper section of the shuttle-shaped exposure cabin, and comprises a columnar guide pipe and a horn cylinder wall; the upper section of the horn cylinder wall is the hollow columnar guide pipe; the columnar guide pipe is inserted into the aerosol inlet sleeve, and the upper section of the horn cylinder wall and the columnar guide pipe together divide an interior space of a lower section of the aerosol inlet sleeve into two isolated gas channels; an inner side surface of the columnar guide pipe and an outer side surface of the horn cylinder wall together form a whole-body exposure diffusion area, i.e., a whole-body exposure channel B, with inner side surfaces of the aerosol inlet sleeve and the exposure cabin; a hollow interior of the horn cylinder wall forms a horn inner cylinder channel; a cylindrical lower guide cylinder, which is a hollow cylinder as a whole and is arranged in the through groove in the middle section of the isolated mouse cage; the hollow cylinder channel is in communication with the horn inner cylinder channel at an upper section and is provided with a plurality of exposure chamber branch pipes leading to front of the exposure chambers; a hollow guide pipe channel in the columnar guide pipe forms an upper section of the horn inner cylinder channel and is in communication with the cylindrical inner cylinder channel and the exposure chamber branch pipes to form a mouth and nose exposure channel A; an exposure channel switching plug, which is a sheet-shaped base plate with a semicircular shape at one end and is provided with a through hole structure at different positions of the sheet-shaped base plate, is arranged in a plug slot in a plug-in manner and is used for switching the mouth and nose exposure channel A and the whole-body exposure channel B; when the mixing and dilution chamber is in communication with the horn inner cylinder channel, the cylindrical inner cylinder channel and the exposure chamber branch pipes through the exposure channel switching plug, an exposure channel for inputting exposure mixed gas into the independent exposure chambers is formed, i.e., the mouth and nose exposure channel A, which is used for implementing a mouth and nose exposure animal experiment; when the mixing and dilution chamber is in communication with the whole-body exposure diffusion area through the exposure channel switching plug, an exposure channel for inputting exposure mixed gas into the independent exposure chambers is formed, i.e., the whole-body exposure channel B, which is used for implementing a whole-body exposure animal experiment. The aerosol inlet sleeve is a hollow cylinder with a closed upper end surface and an open lower end surface, and a plug slot is horizontally arranged on a side surface of the middle section of the hollow cylinder; an upper section of the plug slot is an upper section, and a lower section of the plug slot is a lower section; a center of the upper end surface of the hollow cylinder is provided with an aerosol connecting pipe for connecting an aerosol input pipeline; a clean air connecting pipe for connecting a clean air input pipeline is arranged on a side surface of the upper section of the hollow cylinder; the aerosol connecting pipe and the air connecting pipe are merged above the plug slot to form the mixing and dilution chamber. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 2. The high-reproducibility and high-precision exposure and toxicity animal experiment system according to claim 1, characterized in that, ​ ​ ​ ​ 3. The high-reproducibility and high-precision exposure animal experiment system according to claim 1, characterized in that the trumpet-shaped upper guide cylinder further comprises a hollow horizontal support plate. The hollow horizontal support plate is annular and arranged on the lower end surface of the trumpet cylinder wall. The trumpet cylinder wall is arranged inside the cover-hat-shaped upper cover, and the hollow horizontal support plate is arranged on the outer surface of the bottom of the trumpet cylinder wall and horizontally extends outward and deep, surrounding the trumpet cylinder wall. The trumpet-shaped upper guide cylinder is arranged above the cylindrical lower guide cylinder through the hollow horizontal support plate, so that the trumpet inner cylinder passage and the cylindrical inner cylinder passage are aligned with each other and connected with the isolation cage. The mixed dilution chamber of the aerosol and clean air on the upper section of the aerosol inlet sleeve is connected with one of the two isolated oral-nasal exposure passages A and the whole-body exposure passage B, so as to carry out corresponding exposure experiments.

4. The high-reproducibility and high-precision exposure animal experiment system according to claim 2, characterized in that the exposure passage switching plug is a sheet-shaped substrate with a semicircular shape at one end, and two kinds of switching plugs with through-hole structures are arranged at different positions of the sheet-shaped substrate. The exposure passage switching plug A is a plug A substrate with a semicircular shape, and a center through-hole is arranged at the center of the semicircular shape, and the part of the sheet-shaped substrate around the center through-hole is closed. The exposure passage switching plug B is a plug B substrate with a semicircular shape, and the center of the semicircular shape is closed, and a plum-blossom-shaped through-hole is arranged around the center. A columnar guide pipe is arranged at the center of the trumpet-shaped trumpet cylinder wall, and a guide pipe passage is vertically arranged inside the columnar guide pipe and connected with the trumpet inner cylinder passage inside the trumpet cylinder wall. When the exposure passage switching plug A is inserted into the plug slot, the hollow guide pipe passage inside the columnar guide pipe is opened, so that the oral-nasal exposure passage A is connected with the mixed dilution chamber upward and connected with each exposure chamber downward, and the whole-body exposure diffusion area outside the columnar guide pipe is closed, that is, the entrance of the whole-body exposure passage B is closed, so that the exposure mixed gas of the aerosol and clean air mixed in the mixed dilution chamber is input into each exposure chamber through the exposure chamber branch opening, so as to carry out oral-nasal exposure experiments. When the exposure passage switching plug B is inserted into the plug slot, the whole-body exposure diffusion area outside the columnar guide pipe is opened, so that the whole-body exposure passage B is connected with each exposure chamber, and the guide pipe passage inside the columnar guide pipe is closed, that is, the entrance of the oral-nasal exposure passage A is closed, so that the exposure mixed gas of the aerosol and clean air is input into each exposure chamber from the whole-body exposure diffusion area outside the trumpet cylinder wall in the exposure cabin, so as to carry out whole-body exposure experiments.

5. The high-reproducibility and high-precision exposure animal experiment system according to claim 1, characterized in that the exposure cabin comprises a cover-hat-shaped upper cover, a cylindrical middle cabin surrounding plate, and a funnel-shaped lower cover. ​ ​ ​ The overall profile of the cover-hut-shaped upper cover is conical, and an opening is arranged at the top center of the cover-hut-shaped upper cover, and the lower end surface is an opening, and the conical hollow part inside is an upper section; the lower section of the aerosol gas inlet sleeve is embedded in the opening and extends into the inside of the cover-hut-shaped upper cover, and a sealing ring is arranged in the gap between the aerosol gas inlet sleeve and the opening. The mid-cabin coaming is a vertically arranged cylindrical coaming, and the cylindrical hollow part inside the mid-cabin coaming is a middle section. The overall profile of the funnel-shaped lower cover is funnel-shaped, and the conical hollow part inside is a lower section. The lower end surface of the cover-hut-shaped upper cover is buckled and sealed with the mid-cabin coaming, and the funnel-shaped lower cover and the mid-cabin coaming are an integral structure. The upper section, the middle section and the lower section of the three hollow sections are connected to each other to form a sealed structure inside the exposure chamber, and the isolation cage, the horn-shaped upper guide cylinder and the cylindrical lower guide cylinder are integrally arranged in the sealed structure.

6. The high-repetition and high-precision exposure and poisoning animal experiment system according to claim 5, wherein the isolation cage is a semi-closed cage with a ring-shaped flat cylinder, one side of which is an opening, and a cylindrical through groove is formed in the hollow position around the center, which includes the following mutually buckled metal hole plates: a cage bottom plate, a cage cover plate, an outer cage coaming and a plurality of vertical partitions. The cage bottom plate is a ring-shaped metal hole plate with a through hole at the center, which is arranged on the boss at the joint of the funnel-shaped lower cover and the mid-cabin coaming. The cage cover plate is a ring-shaped metal hole plate formed by splicing a plurality of fan-shaped splicing cover plates, each of which covers a fan-shaped channel of the exposure chamber. The outer cage coaming is a vertical plate arranged between the cage bottom plate and the cage cover plate. The vertical partition is a vertical plate, and a plurality of vertical partitions are symmetrically arranged between the cage bottom plate, the cage cover plate and the outer cage coaming.

7. The high-repetition and high-precision exposure and poisoning animal experiment system according to claim 6, wherein each independent exposure chamber is further provided with a top lifting limiting plate and a front and rear limiting plate to limit the position of the experimental animal; the top lifting limiting plate is suspended on the cage cover plate by lifting bolts and moves up and down to limit the height of the experimental animal in the fan-shaped channel; and the front and rear limiting plate is vertically inserted into the middle of the fan-shaped channel of each exposure chamber to divide the fan-shaped channel into two parts, so that the experimental animal can only move forward in the front part of the fan-shaped channel. ​ ​ ​ When the animal exposure experiment is carried out, the top lifting limiting plate is moved down, the front and rear limiting plate is moved forward, and the experimental animal is limited in the front part of the fan-shaped channel of the exposure chamber, so that the head of the experimental animal is always kept forward, and the experimental animal cannot jump or turn around, and the mouth and nose of the experimental animal are forced to be close to the outlet of the branch pipe of the exposure chamber. When the animal exposure experiment is carried out, the top lifting limiting plate is moved down, the front and rear limiting plate is moved forward, and the experimental animal is limited in the front part of the fan-shaped channel of the exposure chamber, so that the head of the experimental animal is always kept forward, and the experimental animal cannot jump or turn around, and the mouth and nose of the experimental animal are forced to be close to the outlet of the branch pipe of the exposure chamber.

8. The high-reproducibility and high-precision exposure animal experiment system according to claim 6, wherein the cylindrical lower guide cylinder comprises a lower guide cylinder wall and a lower guide cylinder base, a plurality of vertical fins are arranged on the outer side of the lower guide cylinder wall, a cylindrical inner cylinder passage is vertically arranged in the lower guide cylinder wall, the lower end of the cylindrical inner cylinder passage is closed by the lower guide cylinder base, a plurality of exposure chamber branch pipes leading to the exposure chambers are arranged from inside to outside at the position close to the lower guide cylinder base of the cylindrical inner cylinder passage, the inclined cavity between the outer side of the lower guide cylinder wall and the fins forms an exposure chamber diffusion guide groove, and the outer part of the lower guide cylinder wall is communicated with each exposure chamber. The upper end surfaces of the lower guide cylinder wall and the fins are connected with the horn cylinder wall and the hollow horizontal support plate respectively, and the center of the lower guide cylinder wall and the horn cylinder wall is on a vertical line, and the cylindrical inner cylinder passage of the cylindrical lower guide cylinder is communicated with the horn inner cylinder passage. When the cylindrical lower guide cylinder is arranged in the through groove of the isolation cage, the upper and lower end surfaces of the lower guide cylinder wall are flush with the cage bottom plate and the cage cover plate respectively, and the lower guide cylinder wall and the fins close the openings of the exposure chambers towards the center.

9. The high-reproducibility and high-precision exposure animal experiment system according to claim 8, wherein the exposure chamber diffusion guide groove between the outer side of the lower guide cylinder wall and the fins and communicated with the front end of each exposure chamber is used as a feed bin to place the feed of the experimental animal at the position close to the outlet of the exposure chamber branch pipe. A plurality of water bottles with bottle mouths downward are arranged on the hollow horizontal support plate, the water bottles comprise a bottle body, a bottle cap and a water supply pipe, the water supply pipe extends downward into the front part of the fan-shaped channel of each exposure chamber, and the lower end is close to the outlet of the exposure chamber branch pipe to provide drinking water for the experimental animal. The feed bin is arranged with feed, and the water bottles are arranged with drinking water to attract the experimental animal to actively approach the outlet of the exposure chamber branch pipe, so as to improve the total exposure inhalation dose and accuracy. The system further comprises a running support unit connected with the animal exposure experiment unit; The running support unit comprises an air compressor, an aerosol generator, a waste gas treatment module and a negative pressure vacuum pump, which are communicated with each other through connecting pipelines and finally communicated with the exposure chamber respectively; 10. The high-reproducibility and high-precision exposure and toxicity animal experiment system according to any one of claims 1 to 9, characterized in that, The first air path of the air compressor is connected with the aerosol connection pipe of the aerosol inlet sleeve through the MFC and the aerosol generator, and the second air path is connected with the clean air connection pipe of the aerosol inlet sleeve through the clean air MFC. ​ ​ The exhaust treatment module is connected with the lower section of the exposure cabin through an aerosol exhaust pipeline interface, and then connected with the first gas path of the negative pressure vacuum pump through an exhaust MFC.

11. The high-reproducibility and high-precision exposure and toxicity animal experiment system according to claim 10, characterized in that, The system further comprises an operation control unit connected with the exposure cabin, the operation support unit, and the operation control unit; The operation control unit comprises an operation control group and a concentration monitoring group connected through connection lines or pipelines; The operation control group is used for controlling the operation of each part of the exposure cabin and the operation support unit, and comprises a control computer, a single-chip microcomputer controller, an aerosol generator, a clean air MFC, an impact sampler, a particle size spectrometer, an exhaust MFC, and a sampling MFC; The concentration monitoring group is used for real-time feedback, and the input concentration is automatically adjusted by the operation control group after calculation, so as to realize closed-loop control of the exposure cabin and the operation support unit, and comprises a differential pressure sensor, a particulate matter concentration sensor, an oxygen concentration sensor, an impact sampler, and a particle size spectrometer; The control computer is connected with the single-chip microcomputer controller; the single-chip microcomputer controller is connected with the aerosol generator, the clean air MFC, the particle size spectrometer, the exhaust MFC, and the sampling MFC, and connected with the differential pressure sensor, the particulate matter concentration sensor, and the oxygen concentration sensor; One end of each of the differential pressure sensor, the particulate matter concentration sensor, and the oxygen concentration sensor is connected with the single-chip microcomputer controller, and the other end is connected with an aerosol inlet sleeve, so as to collect the pressure difference, the particulate matter concentration, and the oxygen concentration of the mixed gas of the aerosol and the clean air in the mixing and diluting bin; One end of the impact sampler is connected with the exhaust sampling pipeline interface through a gas path, and the other end is connected with the particle size spectrometer and the sampling MFC through a gas path. One end of the particle size spectrometer is connected with the exhaust sampling pipeline interface through a gas path, and the other end is connected with the sampling MFC through a gas path.

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