A bionic alveolar breathing device and a method for constructing an alveolar model

Abstract

The present invention provides a bionic alveolar breathing device and a method for constructing an alveolar model, wherein the bionic alveolar breathing device comprises: a shell; an outer cavity membrane for simulating the thorax, an outer wall chamber is formed between the outer cavity membrane and the shell; a nutrient membrane for simulating blood vessels, an outer cavity chamber is formed between the nutrient membrane and the outer cavity membrane, and the outer cavity chamber simulates the thorax; a bionic alveolar fixing structure, so that the bionic alveoli are located in the nutrient membrane, and a nutrient chamber is formed between the bionic alveoli and the nutrient membrane; a first ventilation tube, simulating a nasal trachea, one end of which is connected to the alveolar cavity of the bionic alveolar; a second ventilation tube, one end of which is connected to the outer wall chamber and the other end is connected to a vacuum generator integrated device to evacuate or pressurize the outer wall chamber; a third ventilation tube, one end of which is connected to the outer cavity chamber and the other end is connected to a carbon dioxide gas source to replace the gas in the outer cavity chamber with carbon dioxide. Beneficial effects: The most realistic breathing environment of the bionic alveoli and the most realistic breathing state of the body can be simulated, and on this basis, alveolar models with different signs can be constructed.

Description

Technical Field

[0001] The invention relates to a bionic alveolar breathing device and a method for constructing an alveolar model. Background Art

[0002] Mechanical ventilation is an intervention measure to save dyspnea caused by lung injury diseases. It can be divided into invasive mechanical ventilation and non-invasive mechanical ventilation in clinical practice. Invasive mechanical ventilation can also cause adverse effects in the treatment of some diseases. It has been found that invasive mechanical ventilation is an independent risk factor for death in COPD patients admitted to the intensive care unit (ICU) for acute respiratory failure. Studies have shown that the main reason for this result is that the tidal volume generated by traumatic mechanical ventilation acts on the alveoli and causes lung damage by forming a certain mechanical force.

[0003] Alveoli are vesicles composed of a single layer of epithelial cells, located around the dilated vesicles at the end of the pulmonary bronchioles. As the basic ventilation unit of the lung, its biomechanical behavior plays an important role in the respiratory physiology of mammals. Alveoli account for more than 70% of the lung volume. During inspiration, the alveoli are stretched and expanded by the stress within the parenchyma to adapt to the inhaled air. During exhalation, the gas is expelled from the lungs by the changes in the pressure of the alveolar environment and its own elastic recoil force. In such a ventilation cycle, the dynamic stress state changes experienced by the alveoli are crucial to better understand the respiratory function of the lung, gas exchange, lung stability, and the mechanism of mechanical ventilation on alveolar injury. It is necessary to study the key determinants of the alveoli during the respiratory cycle, such as the changes in alveolar size and shape caused by alveolar contraction and expansion, the degree of alveolar stretching, and the changes in the number of new alveoli.

[0004] In this regard, the Chinese invention patent with the authorization announcement number CN104316661B discloses a lung tissue model and a method for biological toxicity detection. The lung tissue model includes trachea, blood vessels and alveolar units. The two ends of the trachea are provided with air inlets and air outlets; the two ends of the blood vessels are provided with liquid inlets and liquid outlets; the alveolar unit is a hollow spherical structure with a cavity. The wall of the alveolar unit is an elastic breathable porous membrane. The alveolar unit is arranged in the blood channel and the cavity is connected to the gas channel. The alveolar unit can expand or contract with the change of gas pressure in the gas channel. The gas in the cavity can exchange gas with the gas in the blood channel, realizing the gas exchange function and respiratory strain effect of the lung blood in the body. At the same time, by planting cells in the alveolar unit part, the bionic structure and function of the alveolar unit in the body and the inflammatory response of the immune cells are simulated in the subsequent culture process.

[0005] The above lung tissue model can be used for testing experiments such as the detection of PM2.5 biotoxicity, the detection of drug biotoxicity, and the detection of inhaled drug biotoxicity. However, the lung tissue model only simulates the air intake and exhaust process of the alveoli through the terminal bronchi and the blood environment of the alveoli and outside the alveoli. It does not simulate the changes in alveolar shape and the air intake and exhaust process of the alveoli caused by the rhythmic expansion and contraction of the alveoli outside the alveoli such as the thorax during the breathing process. Therefore, the above lung tissue model cannot simulate the most realistic breathing environment of the alveoli and the most realistic breathing state of the body. Of course, it is also impossible to construct alveolar models with different clinical signs such as normal body alveolar models, thoracic respiratory muscle weakness alveolar models, airway obstruction alveolar models, and pleural effusion alveolar models. On this basis, the reference value of related testing experiments is not high. Summary of the invention

[0006] The purpose of the present invention is to provide a bionic alveolar breathing device that can simulate the most realistic breathing environment of bionic alveoli and the most realistic breathing state of the body; the purpose of the present invention is also to provide a construction method for constructing an alveolar model using the above-mentioned bionic alveolar breathing device, so as to obtain alveolar models with different clinical signs.

[0007] To achieve the above purpose, the bionic alveolar breathing device of the present invention adopts the following technical solutions:

[0008] A bionic alveolar breathing device, comprising:

[0009] case;

[0010] An external cavity membrane is arranged in the shell, the external cavity membrane is used to simulate the thorax, and an external wall chamber is formed between the external cavity membrane and the shell;

[0011] A nutrient membrane is arranged in the outer cavity membrane, the nutrient membrane is used to simulate blood vessels, an outer cavity is formed between the nutrient membrane and the outer cavity membrane, and the outer cavity is used to simulate the chest cavity;

[0012] A bionic alveolar fixing structure is arranged on the shell, and is used to fix the bionic alveoli so that the bionic alveoli are located in the nutrient membrane, and a nutrient chamber for accommodating a culture medium is formed between the bionic alveoli and the nutrient membrane;

[0013] A first ventilation tube is arranged on the shell, the first ventilation tube is used to simulate a nasal trachea, one end of the first ventilation tube is used to communicate with the spherical alveolar cavity of the bionic alveoli, and the other end is used to connect to an air source;

[0014] A second ventilation pipe is arranged on the shell, one end of the second ventilation pipe is connected to the outer wall chamber, and the other end is used to connect the vacuum generator integrated device to evacuate or pressurize the outer wall chamber to expand or contract the outer cavity membrane;

[0015] The third ventilation tube is arranged on the outer cavity membrane. One end of the third ventilation tube is connected to the outer cavity, and the other end is used to connect to the carbon dioxide gas source to replace the gas in the outer cavity with carbon dioxide and simulate the process of human tissue cells producing carbon dioxide after absorbing oxygen.

[0016] The beneficial effects of the above technical solution are: the nutrient membrane is used to simulate blood vessels, the bionic alveolar fixing structure is used to fix the bionic alveoli, so that the bionic alveoli are located in the nutrient membrane, and a nutrient chamber for accommodating the culture medium is formed between the bionic alveoli and the nutrient membrane, thereby simulating the alveoli and the blood environment outside the alveoli, and the first ventilation tube is used to simulate the nasal trachea, so that the air intake and exhaust through the first ventilation tube can simulate the breathing process of the nasal trachea, and in this process, the gas exchange between the spherical alveolar cavity of the bionic alveoli and the nutrient chamber can simulate the external respiration.

[0017] The bionic alveolar breathing device of the present invention also includes an outer cavity membrane for simulating the thorax, the outer cavity membrane is arranged in the shell and is located outside the nutrient membrane, an outer wall chamber is formed between the outer cavity membrane and the shell, an outer cavity chamber is formed between the outer cavity membrane and the nutrient membrane, the outer cavity chamber is used to simulate the thorax, and one end of the second ventilation pipe arranged on the shell is connected to the outer wall chamber, and the other end is used to connect the vacuum generator integrated device, so that the outer wall chamber can be vacuumed or pressed by controlling the exhaust and intake of the second ventilation pipe, and the outer cavity membrane can be expanded or contracted to simulate the breathing process of the thorax. In addition, since one end of the third ventilation pipe arranged on the outer cavity membrane is connected to the outer cavity chamber and the other end is used to connect the carbon dioxide gas source, the gas in the outer cavity chamber can be replaced with carbon dioxide by controlling the intake and exhaust of the third ventilation pipe, simulating the process of human tissue cells producing carbon dioxide after absorbing oxygen, and the gas exchange between the nutrient chamber and the outer cavity can simulate the internal respiration.

[0018] Therefore, the above structural settings can simulate the most realistic breathing environment of the bionic alveoli and the most realistic breathing state of the body. On this basis, alveolar models with different clinical signs such as the normal body alveolar model, the thoracic respiratory muscle weakness alveolar model, the airway obstruction alveolar model and the pleural effusion alveolar model can be constructed. Furthermore, related detection experiments with more reference value can be carried out.

[0019] Furthermore, in order to facilitate the manufacture and installation of the bionic alveolar fixing structure, the bionic alveolar fixing structure includes a fixing tube for the bionic alveolar tube body to penetrate and fix, and a hanging structure for hanging on the shell is arranged on the outer peripheral surface of the fixing tube.

[0020] Furthermore, in order to facilitate the fixation of the bionic alveoli, the length of the fixing tube is shorter than the length of the tube body of the bionic alveoli, so that the tube body passing through the fixing tube can be everted and fixed outside the fixing tube.

[0021] Furthermore, in order to make the volume of each chamber more uniform and improve the accuracy of the experiment, the nutrient membrane, the outer cavity membrane and the shell all have spherical cavities, which are nested layer by layer outside the spherical alveolar cavity of the bionic alveoli.

[0022] Furthermore, in order to facilitate the third ventilation pipe to pass through the shell and connect to the carbon dioxide gas source, the third ventilation pipe passes through the second ventilation pipe.

[0023] Furthermore, in order to facilitate pipeline connection and experiment, the first ventilation pipe is located at the top of the shell, the second ventilation pipe is located at the bottom of the shell, and the third ventilation pipe is located at the bottom of the outer cavity membrane.

[0024] To achieve the above purpose, the method for constructing an alveolar model using the above bionic alveolar breathing device in the present invention adopts the following technical solution:

[0025] The bionic alveoli are nested and fixed on the bionic alveolar breathing device by using a bionic alveolar fixing structure, and the inhalation process of the nasal trachea and the alveolar inhalation process caused by it are simulated by controlling the air intake of the first ventilation tube, and the outer wall chamber is vacuumed and the outer cavity membrane is expanded by controlling the exhaust of the second ventilation tube, so as to simulate the inhalation process of the thorax and the alveolar inhalation process caused by it, and the air intake and exhaust of the third ventilation tube are controlled to replace the gas in the outer cavity with carbon dioxide, so as to simulate the process of human tissue cells producing carbon dioxide after absorbing oxygen, and the exhalation process of the nasal trachea and the alveolar exhalation process caused by it are simulated by controlling the exhaust of the first ventilation tube, and the outer wall chamber is pressurized and the outer cavity membrane is expanded by controlling the air intake and exhaust of the second ventilation tube. The cavity membrane contracts to simulate the exhalation process of the thorax and the alveolar exhalation process caused by it. In the above process, the external respiration is simulated by the gas exchange between the spherical alveolar cavity and the nutrient chamber of the bionic alveoli, and the internal respiration is simulated by the gas exchange between the nutrient chamber and the external chamber, so as to construct a normal body alveolar model capable of nasotracheal breathing, thoracic breathing, and alveolar breathing. Alternatively, an airway obstruction alveolar model is constructed by setting a respiratory obstruction in the first ventilation tube, or a pleural effusion alveolar model is constructed by adding liquid to the external chamber, or a thoracic respiratory muscle weakness alveolar model capable of only nasotracheal breathing and alveolar breathing is constructed by blocking the second ventilation tube and abandoning thoracic respiration.

[0026] The beneficial effects of the above technical solution are: by controlling the air intake and exhaust of the first ventilation tube, the second ventilation tube and the third ventilation tube, the nasotracheal breathing, alveolar breathing and thoracic breathing processes can be simulated, the internal and external respiration of the body can be simulated, and a normal body alveolar model can be constructed; or an airway obstruction alveolar model can be constructed by setting a respiratory obstruction in the first ventilation tube, or a pleural effusion alveolar model can be constructed by adding liquid to the external chamber, or a thoracic respiratory muscle weakness alveolar model that can only perform nasotracheal breathing and alveolar breathing can be constructed by blocking the second ventilation tube and abandoning the thoracic respiration.

[0027] The method for constructing an alveolar model of the present invention can construct alveolar models with different clinical signs, such as a normal body alveolar model, a thoracic respiratory muscle weakness alveolar model, an airway obstruction alveolar model, and a pleural effusion alveolar model. Furthermore, on this basis, relevant detection experiments with greater reference value can be carried out.

[0028] Furthermore, in order to more conveniently construct a normal body alveolar model, by applying at least two different intake and exhaust flow rates to the first ventilation tube, and applying at least two different intake and exhaust flow rates to the second ventilation tube, the nasotracheal breathing and thoracic breathing processes under the action of at least two different flow rate groups are simulated, and finally the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate group are not significantly different from those of the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under the flow rate group are the normal body alveolar model.

[0029] Furthermore, in order to more conveniently construct an alveolar model of thoracic respiratory muscle weakness, at least two different intake and exhaust flow rates are applied to the first ventilation tube to simulate the nasotracheal breathing process under at least two different flow rates, and finally the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate are significantly different from those of zero flow rate without applying a flow rate, the bionic alveolar breathing device and bionic alveoli at this flow rate are an alveolar model of thoracic respiratory muscle weakness.

[0030] Furthermore, in order to more conveniently construct an airway obstruction alveolar model or a pleural effusion alveolar model, by applying at least two different intake and exhaust flow rates to the first ventilation tube, and applying at least two different intake and exhaust flow rates to the second ventilation tube, the nasotracheal breathing and thoracic breathing processes under the action of at least two different flow rate groups are simulated, and finally, the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate group are significantly different from those of the zero flow rate group without applying flow rate, the bionic alveolar breathing device and bionic alveoli under the flow rate group are the airway obstruction alveolar model or the pleural effusion alveolar model. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a schematic diagram of the structure of the bionic alveolar breathing device in the present invention.

[0032] In the figure: 1-first ventilation tube; 2-upper cover; 3-bionic alveoli; 4-nutrient membrane; 5-external cavity membrane; 6-bottom shell; 7-second ventilation tube; 8-third ventilation tube; 9-support leg; 10-outer wall chamber; 11-external cavity; 12-nutrient chamber; 13-spherical alveolar cavity; 14-inner boss; 15-outer boss; 16-hanging ring; 17-hanging arm; 18-fixing tube; 19-end plate. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention, that is, the embodiments described are only part of the embodiments of the present invention, rather than all of the embodiments. The components of the embodiments of the present invention described and shown in the drawings herein can be arranged and designed in various different configurations.

[0034] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work are within the scope of protection of the present invention.

[0035] It should be noted that relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0036] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0037] An embodiment of the bionic alveolar breathing device of the present invention is as follows Figure 1As shown, the housing includes a bottom shell 6 and an upper cover 2. The bottom shell 6 is provided with legs 9. The top of the bottom shell 6 is a columnar structure, and the bottom is a spherical structure. The spherical structure has a spherical cavity. The top of the bottom shell 6 is provided with an end plate 19. The center of the end plate 19 is provided with a circular hole. The end plate 19 is provided with inner bosses 14 and outer bosses 15 from the inside to the outside. The inner bosses 14 and the outer bosses 15 are both annular bosses.

[0038] The upper cover 2 is threadedly connected to the bottom shell 6. Both the bottom shell 6 and the upper cover 2 are made of glass or plastic, which is transparent, strong, sterilizable and easy to process. A first ventilation tube 1 is provided at the top center of the upper cover 2. The first ventilation tube 1 extends up and down, and its bottom end extends downward from the upper cover 2 for a certain length, and most of it is on the upper side of the upper cover 2. The first ventilation tube 1 is used to simulate the nasal trachea. One end of the first ventilation tube 1 is used to communicate with the spherical alveolar cavity of the bionic alveoli, and the other end is used to connect to an air source, and the air source can specifically be an air pump.

[0039] The bionic alveolar breathing device also includes an outer cavity membrane 5 disposed in the bottom shell 6. The outer cavity membrane 5 is a flask-like structure, including a columnar part and a spherical part. The spherical part has a spherical cavity, and the spherical part of the outer cavity membrane 5 is located in the spherical cavity of the bottom shell 6. The top of the columnar part is fixedly sealed and connected to the edge of the circular hole on the end plate 19. The outer cavity membrane 5 is used to simulate the thorax, and is specifically made of polyethylene or polypropylene. The material can be sterilized, can expand and contract under pressure changes, and is transparent and has a certain resilience.

[0040] An outer wall chamber 10 is formed between the outer cavity membrane 5 and the bottom shell 6. A second ventilation pipe 7 extending downward is provided at the bottom of the bottom shell 6. One end of the second ventilation pipe 7 is connected to the outer wall chamber 10, and the other end is used to connect to the vacuum generator integrated device to evacuate or pressurize the outer wall chamber 10 to expand or contract the outer cavity membrane 5.

[0041] The bionic alveolar breathing device also includes a nutrient film 4 disposed in the outer cavity membrane 5. The nutrient film 4 also has a flask-like structure, including a columnar portion and a spherical portion. The spherical portion has a spherical cavity, and the spherical portion of the nutrient film 4 is located in the spherical cavity of the outer cavity membrane 5. The columnar portion of the nutrient film 4 is closely attached to the columnar portion of the outer cavity membrane 5, and the columnar portion of the nutrient film 4 is longer. A hanging ring 16 is fixed to the top of the columnar portion of the nutrient film 4, and the nutrient film 4 is hung on the inner boss 14 through the hanging ring 16.

[0042] The nutrient film 4 is used to simulate blood vessels, and is made of a dialysis membrane or endothelial cell membrane that only allows gas to pass through but does not allow liquid to pass through. An outer chamber 11 is formed between the nutrient film 4 and the outer chamber membrane 5, and the outer chamber 11 is used to simulate the chest cavity. A third ventilation tube 8 extending downward is provided at the bottom of the outer chamber membrane 5, and the third ventilation tube 8 passes through the second ventilation tube 7. One end of the third ventilation tube 8 is connected to the outer chamber 11, and the other end is used to connect to a carbon dioxide gas source, so as to replace the gas in the outer chamber 11 with carbon dioxide, simulating the process of human tissue cells producing carbon dioxide after absorbing oxygen.

[0043] The bionic alveolar breathing device also includes a bionic alveolar fixing structure for fixing the bionic alveoli 3. The bionic alveolar fixing structure in this embodiment includes a fixing tube 18. The bionic alveoli 3 includes a tube body portion and a spherical body portion. The spherical body portion has a spherical alveolar cavity 13, and lung cells grow evenly on the inner wall of the spherical alveolar cavity 13. The tube body portion of the bionic alveoli 3 penetrates into the fixing tube 18, and the tube body portion of the bionic alveoli 3 is longer than the fixing tube 18. The protruding portion, that is, the tube body portion that penetrates the fixing tube 18, is everted and sleeved and fixed to the outside of the fixing tube 18. In order to enhance the fixing effect, a rubber band can be set on the outside of the everted portion.

[0044] A hanging structure is provided on the outer peripheral surface of the fixed tube 18, and the hanging structure is composed of a plurality of hanging arms 17. The hanging arms 17 have three bending structures and are in the shape of a hook. Specifically, the horizontal arm on the outer peripheral surface of the fixed tube 18 extends upward after the first bending, extends laterally outward after the second bending, and finally extends downward after the third bending, so as to be hung on the end plate 19 and limited by the external boss 15.

[0045] After the bionic alveoli 3 are fixed on the fixing tube 18, they are hung on the bottom shell 6 through the hanging arm 17. The spherical part of the bionic alveoli 3 is located in the spherical cavity of the nutrient membrane 4, and a nutrient chamber 12 for accommodating the culture medium is formed between the bionic alveoli 3 and the nutrient membrane 4. After the upper cover 2 is threadedly connected to the bottom shell 6, the bottom end of the first ventilation tube 1 is inserted into a part of the tube body of the bionic alveoli 3 to ensure air tightness. At the same time, in order to enhance the fixing effect of the bionic alveoli 3, the upper cover 2 can be pressed against the bionic alveoli 3.

[0046] An embodiment of the method for constructing an alveolar model using the bionic alveolar breathing device in the present invention is as follows:

[0047] When in use, the accessories related to the bionic alveolar respiration device are sterilized and placed in the clean bench. The legs 9 are placed on the clean bench panel. The legs 9 are used to place the entire bionic alveolar respiration device, and the second ventilation pipe 7 and the third ventilation pipe 8 are kept at a certain distance from the clean bench panel, which is convenient for the later related operations of the second ventilation pipe 7 and the third ventilation pipe 8.

[0048] Epithelial cell culture medium is added into the nutrient film 4 , and then the fixing tube 18 with the bionic alveoli 3 embedded therein is placed on the outside of the outer boss 15 to fix it, and then the upper cover 2 is put on. At this time, the bottom end of the first ventilation tube 1 on the upper cover 2 is embedded in the tube body of the bionic alveoli 3 .

[0049] Next, we will first introduce how the bionic alveolar breathing device imitates the breathing process of the nasotrachea and the thoracic cavity.

[0050] Simulate the inhalation process of a single nasal trachea: When no gas is introduced into the bionic alveoli 3, and the outer chamber 11 and the outer wall chamber 10 are in a closed state, the bionic alveoli 3 presents a collapsed structure due to the pressure of the liquid in the nutrient chamber 12. When the ventilation pump pulses air into the first ventilation tube 1, that is, controls the air intake of the first ventilation tube 1, the spherical alveolar cavity of the bionic alveoli 3 is filled and expanded due to instantaneous inhalation and before the gas penetrates the bionic alveoli 3 (causing the alveolar inhalation process), and when the gas penetrates the bionic alveoli 3, the bionic alveoli slowly rebound due to the change in pressure.

[0051] Gas is introduced through the first ventilation tube 1: first, the air required for the growth of epithelial cells in the bionic alveoli 3 is maintained; second, the bionic alveoli 3 are filled and expanded; third, the epithelial cells of the bionic alveoli 3 are placed in gas on one side and in liquid on the other side, so as to simulate the gas-liquid interface environment of the alveolar cells in the body; fourth, when the oxygen in the air passes through the bionic alveoli 3 to reach the nutrient chamber 12 according to the pressure, penetrates the nutrient membrane 4 to reach the external chamber 11, so as to simulate the process of spontaneous inhalation through the nasal cavity, the oxygen circulates through the trachea-alveoli-blood circulation (nutrient chamber)-peripheral circulation (external chamber), that is, the spontaneous inhalation of the alveoli through the nose, the expansion of the alveoli, and the internal and external inhalation processes are simulated.

[0052] Simulate the inhalation process of adjusting the thorax alone: ​​when no gas is introduced into the bionic alveoli 3, and the outer chamber 11 and the outer wall chamber 10 are in a closed state, the bionic alveoli 3 presents a collapsed structure due to the pressure of the liquid in the nutrient chamber 12. The vacuum generator integrated device is used to pulse the outer wall chamber 10 through the second ventilation tube 7, that is, the exhaust of the second ventilation tube 7 is controlled to reduce the pressure in the outer wall chamber 10, and the outer cavity membrane 5 expands outward under the pressure, so that the pressure in the outer chamber 11 is reduced. By analogy, the spherical alveolar cavity of the bionic alveoli 3 connected to the outside atmosphere is filled or expanded (causing the alveolar inhalation process), and the gas enters the bionic alveoli 3 autonomously and penetrates the bionic alveoli 3 and the nutrient membrane 4 in turn to reach the outer chamber 11, so that the bionic alveoli rebound.

[0053] The pressure is reduced through the second ventilation tube 7: first, gas is introduced into the alveolar cavity to maintain the air required for the growth of epithelial cells; second, the bionic alveoli are enriched and expanded; third, the epithelial cells of the bionic alveoli are placed in gas on one side and in liquid on the other side, so as to simulate the air-liquid interface environment of the alveolar cells in the body; fourth, when the gas passes through the bionic alveoli to reach the nutrient chamber and penetrates the nutrient membrane to reach the external chamber, it simulates the process of passive inhalation through the thorax, and the gas passes through the trachea-alveoli-blood circulation (nutrient chamber)-peripheral circulation (external chamber), that is, it simulates the passive inhalation of the alveoli through the thorax, the expansion of the alveoli, and the internal and external inhalation processes.

[0054] Simulate the inhalation process through the nasotrachea and the thorax: that is, simulate the inhalation process through the nasotrachea alone and simulate the inhalation process by adjusting the thorax alone.

[0055] Simulate the exhalation process of a single nasal trachea: after inhalation, the carbon dioxide gas source connected to the third ventilation tube 8 is used to control the air intake and exhaust of the third ventilation tube 8, and the gas entering the outer chamber 11 is replaced with carbon dioxide, simulating the process of human tissue cells producing carbon dioxide after absorbing oxygen. At this time, the bionic alveoli 3 are in a rebound state.

[0056] The ventilation pump is used to pulse-evacuate the first ventilation tube 1, that is, to control the exhaust of the first ventilation tube 1. Due to instantaneous air extraction and when the carbon dioxide gas has not yet penetrated the nutrient membrane to reach the alveolar cavity, the alveolar cavity contracts (causing the alveolar exhalation process). When carbon dioxide penetrates the bionic alveoli, the bionic alveoli slowly rebound due to the pressure change.

[0057] Air is extracted through the first ventilation tube 1: first, alveolar contraction is achieved; second, one side of the epithelial cells of the bionic alveoli is in gas and the other side is in liquid, so as to simulate the air-liquid interface environment of the alveolar cells in the body; third, when carbon dioxide passes through the nutrient membrane through the external chamber to reach the nutrient chamber according to the pressure, and then passes through the bionic alveolar layer and reaches the alveolar cavity, and is discharged through the first ventilation tube, it is used to simulate the exhalation through the nasal cavity, and the process of carbon dioxide through peripheral circulation (external chamber)-blood circulation (nutrient chamber)-alveoli-trachea, that is, the spontaneous exhalation of the alveoli through the nose, the contraction of the alveoli, and the internal exhalation and external exhalation processes are simulated.

[0058] The exhalation process of adjusting the thorax alone is simulated: after inhalation, the intake and exhaust of the third ventilation tube 8 are controlled by the carbon dioxide gas source connected to the third ventilation tube 8, and the gas entering the outer chamber 11 is replaced with carbon dioxide, simulating the process of human tissue cells producing carbon dioxide after absorbing oxygen. At this time, the bionic alveoli 3 are in a rebound state.

[0059] The vacuum generator integrated device is used to pulse-pressurize the outer wall chamber 10 through the second ventilation tube 7, that is, to control the air intake of the second ventilation tube 7, so that the pressure of the outer wall chamber 10 increases, and then the outer cavity membrane 5 contracts under the action of pressure, the pressure of the outer cavity 11 increases and contracts, and the nutrient membrane and bionic alveoli shrink accordingly (causing the alveolar exhalation process), and carbon dioxide passes through the nutrient membrane-nutrient chamber-bionic alveolar layer-alveolar cavity-first ventilation tube.

[0060] The process includes the replacement of carbon dioxide by the third ventilation tube and the pressurization of the second ventilation tube: first, the pressurization of the second ventilation tube simulates the contraction of the respiratory muscles to change the intrathoracic pressure and the contraction of the chest cavity (contraction of the external chamber); second, it simulates the process of carbon dioxide passing through the periphery (external chamber) - the nutrient chamber (blood circulation) - the alveoli - the trachea, that is, it simulates the contraction of the alveoli and the internal and external exhalation processes when the alveoli exhale gas through the contraction of the chest cavity.

[0061] Simulate the exhalation process through the nasotrachea and the chest: that is, simulate the exhalation process of the nasotrachea alone and simulate the exhalation process of adjusting the chest alone.

[0062] The following constructs the alveolar model under different signs according to the external environment of the alveoli with different signs:

[0063] First, a normal body alveolar model was constructed.

[0064] A normal body is in the process of alveolar respiration caused by the co-inhalation and co-exhalation of the nasal trachea and the thorax, and the bionic alveolar respiration device is in the process of imitating the process of alveolar respiration caused by the co-inhalation and co-exhalation of the nasal trachea and the thorax.

[0065] Low, medium and high pulsed air flow rates were applied through the first ventilation tube, and the air intake and exhaust flow rates of the second ventilation tube were changed accordingly, and the pressurization and depressurization speeds in the outer wall chamber were changed. The bionic alveolar breathing device was in the process of alveolar breathing caused by co-inhalation and co-exhalation of the nasal trachea and the thorax. The contraction of the outer chamber and alveolar cavity under the action of three different flow rate groups was observed, and the culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. The ELISA kit was used to detect the relevant target inflammatory factor indicators (such as IL-6, IL-8, TNF-α, etc.); the oxygen partial pressure and carbon dioxide partial pressure detector were used to detect the oxygen partial pressure and carbon dioxide partial pressure; and the CCK-8 kit was used to detect cytotoxicity.

[0066] When the expression level of inflammatory factors and cytotoxicity of the applied flow rate group are not significantly different from those of the zero flow rate group compared with the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under the flow rate group are the alveolar model of a normal body.

[0067] Second, the alveolar model of thoracic respiratory muscle weakness was constructed.

[0068] When the thoracic muscles are weak, the body has stronger nasal inhalation and exhalation forces, weaker or no thoracic inhalation and exhalation, and the alveoli have inflammatory damage. The bionic alveolar breathing device is only in the process of imitating the alveolar breathing process caused by nasal inhalation and exhalation, and the alveolar cavity cells have inflammatory damage.

[0069] Low, medium and high pulsed air inlet and outlet flow rates are applied through the first ventilation tube respectively to act on the bionic alveoli embedded in the bionic alveolar breathing device, which is in the process of only imitating the alveolar breathing caused by nasal inhalation and exhalation.

[0070] At different flow rates, the contraction of the outer chamber and alveolar cavity was observed, the culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. The ELISA kit was used to detect the relevant target inflammatory factor indicators (such as IL-6, IL-8, TNF-α, etc.); the oxygen partial pressure and carbon dioxide partial pressure detector were used to detect the oxygen partial pressure and carbon dioxide partial pressure; the CCK-8 kit was used to detect cytotoxicity.

[0071] Compared with zero flow rate without applied flow rate, when the expression levels of cytotoxicity and inflammatory factors in the applied flow rate group are significantly different from those in the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under this flow rate are alveolar models of thoracic respiratory muscle weakness.

[0072] Third, the alveolar model with airway obstruction was constructed.

[0073] The airway is blocked, the body's nasal inhalation and exhalation are weak, the thoracic inhalation and exhalation are strong, and the alveoli are inflammatory and damaged. The bionic alveolar breathing device is in the process of imitating the alveolar breathing process caused by nasal and thoracic co-inhalation and co-exhalation, and the alveolar cavity cells are inflammatory and damaged, and the middle section of the first ventilation tube is equipped with a respiratory obstruction, which can be sterile cotton.

[0074] Low, medium and high pulsed air flow rates were applied through the first ventilation tube, and the air intake and exhaust flow rates of the second ventilation tube were changed accordingly, and the pressurization and depressurization speeds in the outer wall chamber were changed. The bionic alveolar breathing device was in the process of alveolar breathing caused by co-inhalation and co-exhalation of the nasal trachea and the thorax. The contraction of the outer chamber and alveolar cavity under the action of three different flow rate groups was observed, and the culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. The ELISA kit was used to detect the relevant target inflammatory factor indicators (such as IL-6, IL-8, TNF-α, etc.); the oxygen partial pressure and carbon dioxide partial pressure detector were used to detect the oxygen partial pressure and carbon dioxide partial pressure; and the CCK-8 kit was used to detect cytotoxicity.

[0075] When the expression level of inflammatory factors and cytotoxicity in the applied flow rate group are significantly different from those in the zero flow rate group compared with the zero flow rate group, the bionic alveolar breathing device and bionic alveoli in the flow rate group are alveolar models with airway obstruction.

[0076] Fourth, the alveolar model of pleural effusion was constructed.

[0077] The body with pleural effusion is in the process of alveolar respiration caused by co-inhalation and co-exhalation of the nose and thorax, and there is effusion in the pleural cavity and inflammation of the alveoli. The bionic alveolar respiration device is in the process of alveolar respiration caused by co-inhalation and co-exhalation of the nose and thorax, and different volumes of liquid are added to the outer chamber.

[0078] Low, medium and high pulsed air flow rates were applied through the first ventilation tube, and the air intake and exhaust flow rates of the second ventilation tube were changed accordingly, and the pressurization and depressurization speeds in the outer wall chamber were changed. The bionic alveolar breathing device was in the process of alveolar breathing caused by co-inhalation and co-exhalation of the nasal trachea and the thorax. The contraction of the outer chamber and alveolar cavity under the action of three different flow rate groups was observed, and the culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. The ELISA kit was used to detect the relevant target inflammatory factor indicators (such as IL-6, IL-8, TNF-α, etc.); the oxygen partial pressure and carbon dioxide partial pressure detector were used to detect the oxygen partial pressure and carbon dioxide partial pressure; and the CCK-8 kit was used to detect cytotoxicity.

[0079] When the expression level of inflammatory factors and cytotoxicity of the applied flow rate group are significantly different from those of the zero flow rate group compared with the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under the flow rate group are the pleural effusion alveolar model.

[0080] Based on the successful construction of the above-mentioned normal body alveolar model, thoracic respiratory muscle weakness alveolar model, airway obstruction alveolar model and pleural effusion alveolar model, experiments were carried out to detect the effects of mechanical ventilation on alveolar models with different signs, the damage and beneficial effects of tobacco product aerosols on alveoli under different signs, the damage and beneficial effects of aerosol drugs on alveoli under different signs, and the alveolar deposition sites of aerosols of different particle sizes under different signs.

[0081] First, the effect of mechanical ventilation on alveolar models with different signs.

[0082] The first ventilation tube of the alveolar model with different signs was exposed to the air-liquid interface by ventilation at large, medium, small, and zero flow rates. After ventilation for a certain period of time (1, 3, and 6 hours), the contraction of the outer chamber and alveolar cavity was observed at different flow rates and action times. The culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. ELISA kits, biochemical analyzers, etc. were used to detect relevant immune indicators (such as IL-6, IL-8, TNF-α, etc.) and biochemical indicators; oxygen partial pressure and carbon dioxide partial pressure detectors were used to detect oxygen partial pressure and carbon dioxide partial pressure; CCK-8 kits were used to detect cytotoxicity; PCR and Western blot methods were used to detect relevant target genes and proteins.

[0083] Determine the damage and beneficial effects of different mechanical forces on alveoli under different signs: Compared with the zero ventilator mechanical force flow rate group, the significantly reduced cell survival rate and significantly increased expression of inflammatory factors indicate that the mechanical force flow rate group has damage to the bionic alveoli under this sign; the significantly increased cell survival rate and significantly reduced expression of inflammatory factors indicate that the mechanical force flow rate group is beneficial to the bionic alveoli under this sign. Changes in biochemical indicators, target genes and target proteins should be explained according to specific questions.

[0084] Second, the damaging and beneficial effects of tobacco product aerosol on alveoli under different signs.

[0085] The first ventilation tube of the alveolar model with different signs was exposed to the air-liquid interface by large, medium and small puffs of smoke aerosol and large, medium and small puffs of air. After a certain number of puffs, the contraction of the outer chamber and alveolar cavity was observed at different puffs. The culture medium in the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas in the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. ELISA kits, biochemical analyzers, etc. were used to detect relevant immune indicators (such as IL-6, IL-8, TNF-α, etc.) and biochemical indicators; oxygen partial pressure and carbon dioxide partial pressure detectors were used to detect oxygen partial pressure and carbon dioxide partial pressure; CCK-8 kits were used to detect cytotoxicity; PCR and Western blot methods were used to detect relevant target genes and proteins.

[0086] Determine the damage and beneficial effects of tobacco product aerosol on bionic alveoli under different signs: compared with the air group with the same number of puffs, the significantly reduced cell survival rate and significantly increased expression of inflammatory factors indicate that the smoke puff group has damaged the bionic alveoli under the sign; the significantly increased cell survival rate and significantly reduced expression of inflammatory factors indicate that the smoke puff group is beneficial to the bionic alveoli under the sign. Changes in biochemical indicators, target genes and target proteins should be explained according to specific questions.

[0087] Since tobacco smoke is an aerosol, this method can be applied to exposure to exogenous harmful aerosol substances such as PM2.5 through inhalation.

[0088] Third, the damage and beneficial effects of aerosol drugs on alveoli under different signs.

[0089] The first ventilator of the alveolar model with different signs was exposed to the air-liquid interface by passing large, medium, small and zero doses of aerosol drugs. After a certain period of exposure, the contraction of the outer chamber and alveolar cavity was observed at different doses, the culture medium of the nutrient chamber was collected for the detection of inflammatory factor indicators, the gas of the outer chamber was collected for the detection of oxygen partial pressure and carbon dioxide partial pressure, and the cells on the bionic alveoli were collected for the detection of cytotoxicity. ELISA kits, biochemical analyzers, etc. were used to detect relevant immune indicators (such as IL-6, IL-8, TNF-α, etc.) and biochemical indicators; oxygen partial pressure and carbon dioxide partial pressure detectors were used to detect oxygen partial pressure and carbon dioxide partial pressure; CCK-8 kits were used to detect cytotoxicity; PCR and Western blot methods were used to detect relevant target genes and proteins.

[0090] Determine the damage and beneficial effects of aerosol drugs on bionic alveoli under different signs: compared with zero dose, the significant decrease in cell survival rate and the significant increase in inflammatory factor expression indicate that this dose group has damage to the bionic alveoli under this sign; the significant increase in cell survival rate and the significant decrease in inflammatory factor expression indicate that this dose group is beneficial to the bionic alveoli under this sign. Changes in biochemical indicators, target genes and target proteins should be explained according to specific questions.

[0091] Fourth, the alveolar deposition sites of aerosols of different particle sizes under different signs.

[0092] Different color-coded aerosols of different particle sizes were introduced into the first ventilation tube of the alveolar models with different signs for air-liquid interface exposure. After a certain period of exposure, the contraction of the outer chamber and alveolar cavity was observed under different particle sizes, and the color of the bionic alveoli and bionic alveolar respiratory devices such as the nutrient membrane, the outer chamber membrane, and the outer chamber was observed to see if there were any changes; when the color observation was not obvious, the nutrient chamber liquid and the outer chamber gas were collected, and the liquid was collected after each layer of the membrane was washed with sterile water.

[0093] Determine the alveolar deposition site of aerosols of different particle sizes under different signs: observe whether the color of the bionic alveoli and bionic alveolar respiratory devices such as the nutrient membrane, the outer cavity membrane, and the outer cavity changes. The site with color change indicates that the aerosol of the corresponding color is deposited, and the site without color change has no deposition. Use a particle size detector to detect the particle size in the collected gas and liquid to determine the level of penetration of aerosols of different particle sizes and properties under different signs.

[0094] Finally, using the above concept, the alveolar expansion and contraction ratios under different ventilation conditions on a multi-alveolar model with different signs can also be detected.

[0095] Firstly, according to the external environment of the alveoli with different signs, alveolar models with different signs are established in the same way as above, and the bionic alveoli embedded in the bionic alveolar breathing device are multi-bionic alveoli with multiple spherical alveolar cavities.

[0096] Secondly, the effects of different ventilation on multi-alveolar models with different signs. The first ventilation tube was exposed to the air-liquid interface by using a ventilator to pass large, medium, small, and zero ventilation flow rates, and the degree and number of multi-alveolar expansion and contraction were observed during ventilation.

[0097] Determine the expansion and contraction of multiple alveoli under different ventilation and different signs: calculate the ratio of the number of expanded and contracted alveoli to the total number of alveoli, as well as the ratio of the degree of alveolar expansion and contraction to the normal volume, in order to understand the degree and ratio of alveolar expansion and contraction in the body under different ventilation.

[0098] In other embodiments of the method for constructing an alveolar model, in the method for constructing an alveolar model with different physical signs, two flow rate groups with different flow rates may also be set, and of course four or more groups may also be set.

[0099] In other embodiments of the method for constructing an alveolar model, in the method for constructing alveolar models with different signs, whether the alveolar models with different signs are successfully constructed is not determined by comparing different flow rate groups with a zero flow rate group, but by directly determining the flow rate group through scientific calculations.

[0100] In other embodiments of the method for constructing an alveolar model, when constructing an airway obstruction alveolar model, the respiratory obstruction provided in the first ventilation tube may also be a sponge or a cloth.

[0101] In other embodiments of the bionic alveolar respiration device, the second ventilation tube may also be arranged on the side of the bottom shell, for example, extending laterally; the third ventilation tube may also be arranged on the side of the outer cavity membrane, for example, extending laterally; the third ventilation tube may not pass through the second ventilation tube, but pass through the bottom shell alone; when the bionic alveolar respiration device can be placed horizontally, it can be considered that the first ventilation tube is arranged on the side of the shell.

[0102] In other embodiments of the bionic alveolar respiratory device, the nutrient membrane, the outer cavity membrane and the shell may not have a spherical cavity, but may be a columnar structure.

[0103] In other embodiments of the bionic alveolar breathing device, the length of the fixed tube may also be equal to the length of the tube body of the bionic alveolar, and the tube body of the bionic alveolar may be bonded and fixed to the tube opening of the fixed tube.

[0104] In other embodiments of the bionic alveolar respiratory device, the hanging structure on the fixed tube can be an L-shaped structure, which is bent only once. Specifically, the horizontal side of the L-shaped structure is connected to the fixed tube, and the vertical side is hung on the end plate and limited by the external boss.

[0105] In other embodiments of the bionic alveolar respiration device, when the width of the inner boss is sufficient, the hanging arm may also be hung on the outer side of the inner boss, and in this case, there is no need to provide an outer boss.

[0106] In other embodiments of the bionic alveolar breathing device, the first ventilation tube can extend downward beyond the upper cover to a greater length, so that the first ventilation tube serves as a bionic alveolar fixing structure. At this time, the tube body of the bionic alveolar passes through the first ventilation tube and is everted and fixed outside the first ventilation tube.

[0107] In other embodiments of the bionic alveolar respiratory device, when the nutrient membrane can fix the tubular body portion of the bionic alveoli, the nutrient membrane can also be used as a bionic alveolar fixing structure.

[0108] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. The patent protection scope of the present invention shall be based on the claims. All equivalent structural changes made using the contents of the description and drawings of the present invention should also be included in the protection scope of the present invention.

Claims

1. A bionic alveolar breathing device, characterized in that: include: case; An external cavity membrane is arranged in the shell, the external cavity membrane is used to simulate the thorax, and an external wall chamber is formed between the external cavity membrane and the shell; A nutrient membrane is arranged in the outer cavity membrane, the nutrient membrane is used to simulate blood vessels, an outer cavity is formed between the nutrient membrane and the outer cavity membrane, and the outer cavity is used to simulate the chest cavity; A bionic alveolar fixing structure is arranged on the shell, and is used to fix the bionic alveoli so that the bionic alveoli are located in the nutrient membrane, and a nutrient chamber for accommodating a culture medium is formed between the bionic alveoli and the nutrient membrane; A first ventilation tube is arranged on the shell, the first ventilation tube is used to simulate a nasal trachea, one end of the first ventilation tube is used to communicate with the spherical alveolar cavity of the bionic alveoli, and the other end is used to connect to an air source; A second ventilation pipe is arranged on the shell, one end of the second ventilation pipe is connected to the outer wall chamber, and the other end is used to connect the vacuum generator integrated device to evacuate or pressurize the outer wall chamber to expand or contract the outer cavity membrane; A third ventilation tube is arranged on the outer cavity membrane, one end of the third ventilation tube is connected to the outer cavity, and the other end is used to connect to the carbon dioxide gas source, so as to replace the gas in the outer cavity with carbon dioxide, simulating the process of human tissue cells producing carbon dioxide after absorbing oxygen, and the third ventilation tube passes through the second ventilation tube; The nutrient membrane, the outer cavity membrane and the shell are all in columnar structure or the nutrient membrane, the outer cavity membrane and the shell have spherical cavity, so as to be nested layer by layer outside the spherical alveolar cavity of the bionic alveoli.

2. The bionic alveolar breathing device according to claim 1, characterized in that: The bionic alveolar fixing structure comprises a fixing tube for the tube body of the bionic alveolar to penetrate and fix, and a hanging structure for hanging on a shell is arranged on the outer peripheral surface of the fixing tube.

3. The bionic alveolar breathing device according to claim 2, characterized in that: The length of the fixing tube is shorter than the length of the tube body of the bionic alveolar, so that the tube body passing through the fixing tube can be everted and sleeved and fixed outside the fixing tube.

4. The bionic alveolar breathing device according to any one of claims 1 to 3, characterized in that: The first ventilation tube is located at the top of the shell, the second ventilation tube is located at the bottom of the shell, and the third ventilation tube is located at the bottom of the outer cavity membrane.

5. A method for constructing an alveolar model using the bionic alveolar breathing device according to claim 1, characterized in that: The bionic alveoli are nested and fixed on the bionic alveolar breathing device by using a bionic alveolar fixing structure, and the inhalation process of the nasal trachea and the alveolar inhalation process caused by it are simulated by controlling the air intake of the first ventilation tube, and the outer wall chamber is vacuumed and the outer cavity membrane is expanded by controlling the exhaust of the second ventilation tube, so as to simulate the inhalation process of the thorax and the alveolar inhalation process caused by it, and the air intake and exhaust of the third ventilation tube are controlled to replace the gas in the outer cavity with carbon dioxide, so as to simulate the process of human tissue cells producing carbon dioxide after absorbing oxygen, and the exhalation process of the nasal trachea and the alveolar exhalation process caused by it are simulated by controlling the exhaust of the first ventilation tube, and the outer wall chamber is pressurized and the outer cavity membrane is expanded by controlling the air intake and exhaust of the second ventilation tube. The cavity membrane contracts to simulate the exhalation process of the thorax and the alveolar exhalation process caused by it. In the above process, the external respiration is simulated by the gas exchange between the spherical alveolar cavity and the nutrient chamber of the bionic alveoli, and the internal respiration is simulated by the gas exchange between the nutrient chamber and the external chamber, so as to construct a normal body alveolar model capable of nasotracheal breathing, thoracic breathing, and alveolar breathing. Alternatively, an airway obstruction alveolar model is constructed by setting a respiratory obstruction in the first ventilation tube, or a pleural effusion alveolar model is constructed by adding liquid to the external chamber, or a thoracic respiratory muscle weakness alveolar model capable of only nasotracheal breathing and alveolar breathing is constructed by blocking the second ventilation tube and abandoning thoracic respiration.

6. The method for constructing an alveolar model according to claim 5, characterized in that: By applying at least two different intake and exhaust flow rates to the first ventilation tube, and applying at least two different intake and exhaust flow rates to the second ventilation tube, the nasotracheal breathing and thoracic breathing processes under the action of at least two groups of different flow rate groups are simulated, and finally the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate group are not significantly different from those of the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under the flow rate group are the alveolar model of a normal body.

7. The method for constructing an alveolar model according to claim 5 or 6, characterized in that: By applying at least two different intake and exhaust flow rates to the first ventilation tube, the nasotracheal breathing process under at least two different flow rates is simulated, and finally the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate are significantly different from those of zero flow rate without applying a flow rate, the bionic alveolar breathing device and bionic alveoli at this flow rate are alveolar models of weak thoracic respiratory muscles.

8. The method for constructing an alveolar model according to claim 5 or 6, characterized in that: By applying at least two different intake and exhaust flow rates to the first ventilation tube, and applying at least two different intake and exhaust flow rates to the second ventilation tube, the nasotracheal breathing and thoracic breathing processes under the action of at least two different flow rate groups are simulated, and finally the inflammatory factor indicators of the culture medium in the nutrient chamber and the cytotoxicity of the cells on the bionic alveoli are detected. When the inflammatory factor expression level and cytotoxicity of the applied flow rate group are significantly different from those of the zero flow rate group, the bionic alveolar breathing device and bionic alveoli under the flow rate group are airway obstruction alveolar models or pleural effusion alveolar models.

Images