Construction method and application of COPD mouse model

Abstract

The invention discloses a construction method and application of a COPD mouse model, and the construction method of the COPD mouse model comprises the following steps: instilling an LPS solution into the trachea of a mouse for the first time on the first day; first-stage feeding is conducted on the mice one day after the LPS solution is dripped for the first time, the first-stage feeding lasts for 7-16 days, and the mice are continuously exposed in the smoke environment to be fed; on the first day after the first-stage feeding is finished, instilling the LPS solution into the trachea of the mouse for the second time; carrying out second-stage feeding on the mice one day after the LPS solution is instilled for the second time, keeping the second-stage feeding for 10-15 weeks, and continuously exposing the mice in the smoke environment for feeding; the COPD mouse model is obtained. Through specific parameter setting of the LPS combined CS system and staged feeding of the mice, the method has the advantages that the mouse COPD model can be copied with high efficiency and high model forming rate, the animal death rate is extremely low, errors are avoided, and the method conforms to the actual consumption behavior habits of tobacco and the clinical COPD pathogenesis process.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a method for constructing a COPD mouse model and its application. Background Technology

[0002] Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow limitation and respiratory symptoms. The etiology of COPD is complex, but its essence is a chronic inflammatory response centered on the airways, lung parenchyma, and pulmonary vessels. Exposure to exogenous factors such as cooking fumes, vehicle exhaust, smog, bacterial and viral infections, and cigarette smoke are all important factors that induce or aggravate COPD.

[0003] Currently, COPD has become the third leading cause of death worldwide, with many patients suffering from COPD for decades and dying prematurely due to the disease itself or its complications. The establishment of COPD animal models is a crucial foundation for conducting animal experiments to study the etiology and treatment of COPD, playing an irreplaceable role in COPD research. Therefore, establishing animal models that meet clinical standards is of great significance.

[0004] In previous studies on COPD model preparation, most methods employed single cigarette smoke (CS) exposure for model establishment. However, this method typically requires 24 weeks or more to produce a relatively stable COPD model, and suffers from problems such as an excessively long model establishment period, numerous confounding factors, and relatively mild alveolar lesions.

[0005] A small number of cases use intratracheal injection of lipopolysaccharide (LPS) to create a model. LPS is an active ingredient unique to the outer wall of Gram-negative bacteria, which can cause airway epithelial damage and induce airway inflammation. However, this method overemphasizes the inflammatory response and ignores the main cause. None of the above methods are consistent with the multifactorial pathogenesis of COPD.

[0006] Recent research advocates for a more accurate approach to COPD modeling using a combined LPS+CS induction method. However, most studies employing this method overemphasize short experimental periods, typically around one month. While these studies have observed significant inflammatory and pathological changes, they lack a comprehensive analysis of the model's pathological structure and lung function to determine its clinical suitability.

[0007] In general clinical diagnosis, a lung function FEV1 / FVC% <70% is considered the gold standard, with patient history and precipitating factors serving as supplementary diagnostic criteria. Previous researchers, while conducting lung function tests, often failed to utilize the crucial indicator of small airway resistance, FEV0.1 / FVC%, or obtained lung function test results significantly exceeding the clinical diagnostic standard of FEV1 / FVC% <70%, thus failing to reflect clinical reality. Animal models that do not meet clinical standards can greatly affect the reliability of pharmacodynamic and other experimental results.

[0008] Furthermore, existing technologies often involve constructing mouse models using self-made full-body exposure fumigation chambers. The test results are easily affected by the full-body exposure of the mice, leading to errors. Moreover, the flue gas parameters are uncontrollable, and the animal's exhaled exhaust gas pollutes and dilutes the flue gas exposure environment, making it impossible to accurately study the mechanism of COPD mouse models.

[0009] Therefore, there is an urgent need to develop stable, efficient methods for preparing animal models that conform as closely as possible to the clinical pathological changes in human COPD. Summary of the Invention

[0010] The purpose of this invention is to provide a method for constructing a COPD mouse model and its application, thereby solving the technical problems of existing COPD animal models, such as long construction time, poor stability, high mortality, and failure to meet the clinical requirements for multifactorial pathogenesis.

[0011] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0012] A method for constructing a COPD mouse model includes the following steps:

[0013] Step S1: On day 1, LPS solution was instilled into the trachea of ​​the mice for the first time;

[0014] Step S2: Starting one day after the first infusion of LPS solution, mice were fed in the first stage of feeding, which lasted for 7 to 16 days, during which the mice were continuously exposed to the flue gas environment.

[0015] Step S3: On the first day after the end of the first stage of feeding, LPS solution was administered to the trachea of ​​the mice for the second time.

[0016] Step S4: Starting one day after the second infusion of LPS solution, mice were fed in the second stage of feeding for 10 to 15 weeks, during which they were continuously exposed to the flue gas environment.

[0017] Step S5: Obtain the COPD mouse model.

[0018] Furthermore, the mice were adult mice aged 6-8 weeks from the C57 / BL-6 strain.

[0019] Furthermore, in step S2, the continuous exposure of mice to the smoke environment includes the following steps:

[0020] Step S21: Expose the mice to the mainstream cigarette smoke environment at a fixed time in the morning for 1 to 3 hours;

[0021] Step S22: The mice obtained in step S21 are subjected to smokeless treatment for 2-4 hours.

[0022] Step S23: Expose the mice obtained in step S22 to the mainstream cigarette smoke environment again for 1 to 3 hours.

[0023] Furthermore, during the first phase of feeding, the average total particulate matter concentration in the mainstream cigarette smoke environment was maintained at 30–50 mg / m³. 3 between.

[0024] Furthermore, during the second phase of feeding, the average total particulate matter concentration in the mainstream cigarette smoke environment was maintained at 140–160 mg / m³. 3 between.

[0025] Furthermore, the tar content in the mainstream cigarette smoke environment is 10 mg / m³. 3 .

[0026] Furthermore, the first infusion of LPS solution includes the following steps:

[0027] Step S11: Anesthetize the mice with sodium pentobarbital.

[0028] Step S12: Expose the trachea of ​​the anesthetized mouse and slowly drip LPS solution into the airway of the mouse through a soft tube with a guide wire. The injection dose of LPS solution is 6-8 μL / mouse.

[0029] Step S13: Rotate and shake the mouse obtained in step S12 to allow the LPS solution to enter all parts of the lungs evenly.

[0030] Furthermore, the second LPS solution infusion procedure is the same as the first LPS solution infusion procedure.

[0031] The present invention also provides an application of a flue gas system combined with lipopolysaccharide in any of the above-mentioned COPD mouse models.

[0032] Furthermore, the flue gas system is the HRH-MNE3026 small animal single-concentration oral-nasal exposure system, which effectively avoids errors caused by whole-body exposure of mice to a flue gas environment. This invention utilizes the HRH-MNE3026 small animal single-concentration oral-nasal exposure system (hereinafter referred to as the CS system) for oral-nasal exposure and intratracheal instillation of lipopolysaccharide (LPS). LPS was instilled intratracheally in mice on days 1 and 14, and the mice were subjected to daily flue gas exposure using the CS system for 12 weeks to obtain a COPD animal model.

[0033] Furthermore, the flue gas system can create a stable and controllable flue gas environment through parameter settings.

[0034] Furthermore, the flue gas concentration in the flue gas system can be set.

[0035] Furthermore, the mice did not contaminate the diluted smoke environment.

[0036] Furthermore, the exposure time of mice in the mainstream cigarette smoke environment can be set through the smoke system.

[0037] Furthermore, the flue gas system parameters include: an upper temperature limit of 25.00℃, a lower temperature limit of 19.00℃, an upper humidity limit of 70.00%RH, a lower humidity limit of 30.00%RH, an upper pressure limit of 50.00Pa, a lower pressure limit of 0.00Pa, an upper oxygen concentration limit of 25.00%, a lower oxygen concentration limit of 19.00%, an upper carbon dioxide concentration limit of 1.000%, and a lower carbon dioxide concentration limit of 0.000%.

[0038] Furthermore, the dilution flow rate of the flue gas system is set to 5.00–15.00 L / min, the extraction flow rate is set to 5.00–10.00 L / min, and the pressure difference is set to 5.00–20.00 Pa.

[0039] This invention further claims a method for screening drugs for the treatment and / or prevention of COPD, the method comprising the following steps:

[0040] Step 1): Apply the drug to be tested to the mouse model constructed by any of the above methods;

[0041] Step 2): Analyze and evaluate the therapeutic effects of the test drugs, and select test drugs that can significantly improve the pathological characteristics of COPD in mouse models.

[0042] The present invention aims to provide a rapid, stable, and efficient animal model that better reflects the multifactorial pathogenesis of clinical COPD. The COPD mouse model constructed by the present invention can detect FEV90 / FVC%, PEF, and RI, making the mouse lung function test indicators more comprehensive and of greater reference value.

[0043] Lipopolysaccharide (LPS) is an endotoxin that exhibits a variety of biological activities when acting on cells in humans, animals, and other organisms. Intratracheal instillation of LPS leads to the activation of various inflammatory cells and the release of cytokines, further exacerbating lung inflammation and causing damage to the airway and alveolar epithelium. This invention utilizes LPS combined with the CS system to induce a COPD disease model, which can be used for research on the pathogenesis of COPD and evaluation of the efficacy of COPD treatment drugs, showing promising application prospects.

[0044] Compared to existing COPD animal induction models, this invention, through specific parameter settings of the LPS combined with the CS system and staged feeding of mice, can efficiently and successfully replicate a mouse COPD model. This modeling method has a series of advantages, including stable and controllable smoke concentration and exposure time, extremely low animal mortality, avoidance of errors caused by systemic smoke exposure through oral and nasal inhalation, avoidance of pollution and dilution of the smoke exposure environment by animal exhaled exhaust gas, and conformity with actual tobacco consumption habits and the clinical course of COPD. It has great application potential and broad promotion value. Attached Figure Description

[0045] The above description of the present invention and the following detailed embodiments will be better understood when read in conjunction with the accompanying drawings. It should be noted that the drawings are merely examples of the claimed technical solutions.

[0046] Figure 1A This is a flowchart illustrating the steps of administering lipopolysaccharide S11 via intratracheal instillation to model mice according to one embodiment of the present invention.

[0047] Figure 1B This is a flowchart illustrating the steps of administering lipopolysaccharide S12 via intratracheal instillation to model mice according to one embodiment of the present invention.

[0048] Figure 1C This is an injection operation diagram of the steps for administering lipopolysaccharide S12 via intratracheal drip to model mice according to one embodiment of the present invention.

[0049] Figure 2 This is a schematic diagram of a CS system according to one embodiment of the present invention;

[0050] Figure 3 This is a parameter setting diagram of a CS system according to one embodiment of the present invention;

[0051] Figure 4A This is a comparison diagram of HE staining results of model mice exposed to flue gas for 4 weeks and control mice fed normally for 4 weeks according to one embodiment of the present invention.

[0052] Figure 4BThis is a comparison diagram of HE staining results of model mice exposed to flue gas for 8 weeks and control mice fed normally for 8 weeks according to one embodiment of the present invention.

[0053] Figure 4C This is a comparison diagram of HE staining results of model mice exposed to flue gas for 12 weeks and control mice fed normally for 12 weeks according to one embodiment of the present invention.

[0054] Figure 5A This is a comparison chart of the FEV90 / FVC results of a model group of mice exposed to flue gas for 12 weeks and a control group of mice fed normally for 12 weeks, according to one embodiment of the present invention.

[0055] Figure 5B This is a comparison chart of PEF results between a model group of mice exposed to flue gas for 12 weeks and a control group of mice fed normally for 12 weeks, according to one embodiment of the present invention.

[0056] Figure 5C This is a comparison chart of the RI results of a model group of mice exposed to flue gas for 12 weeks and a control group of mice fed normally for 12 weeks, according to one embodiment of the present invention.

[0057] Figure 5D This is a comparison chart of Cdyn results for model mice exposed to flue gas for 12 weeks and control mice fed normally for 12 weeks, according to one embodiment of the present invention. Detailed Implementation

[0058] The following detailed description of the features and advantages of the present invention is sufficient to enable any person skilled in the art to understand the technical content of the present invention and implement it accordingly. Furthermore, based on the specification, claims and drawings disclosed herein, those skilled in the art can easily understand the related objects and advantages of the present invention.

[0059] It should be noted that in this specification, similar reference numerals and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0060] In the description of this embodiment, it should be noted that the terms "upper", "lower", "inner", "bottom", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product is usually placed during use. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting the present invention.

[0061] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0062] It should be noted that the mice used in this embodiment were purchased from a compliant and legal experimental animal production company and housed in an SPF-grade animal facility.

[0063] The instruments and apparatus involved in the embodiments of the present invention are as follows:

[0064] HRH-MNE3026 Small Animal Single-Concentration Oral-Nasal Exposure System;

[0065] Ten-channel rotary smoke extractor.

[0066] The reagents and materials involved in the embodiments of this invention are as follows:

[0067] Traditional cigarettes (tar content 10mg);

[0068] Sodium pentobarbital;

[0069] Lipopolysaccharide (LPS).

[0070] The present invention discloses a method for constructing a COPD mouse model, which includes the following steps: LPS is instilled into the trachea of ​​mice on days 1 and 14, respectively, and the mice are exposed to CS system flue gas for 12 weeks to obtain a COPD animal model.

[0071] In the endotracheal instillation of LPS, mice are anesthetized with 1% sodium pentobarbital, their trachea is exposed, and LPS solution is slowly dripped into the airway of the mice through a soft tube with a guidewire. The mice are then rotated and shaken to ensure that the lipopolysaccharide is evenly distributed into all parts of the lungs.

[0072] The mice used were C57 / BL-6 strain mice, preferably adult mice aged 6-8 weeks.

[0073] As shown in Figures 1-5, one embodiment of the present invention provides a method for establishing a COPD model using a flue gas system combined with lipopolysaccharide induction. This method includes intratracheal infusion of medication and setting parameters for the CS system. The operation flow and actual operation are shown in Figures 1-3, respectively, and specifically include the following steps:

[0074] Adult C57 / BL-6 mice, aged 6-8 weeks, were used. Mice were weighed and housed in individual cages in an SPF-grade animal facility, ensuring free movement, access to food and water, and were labeled as the model group mice. LPS solution was administered intratracheally to the model group mice on days 1 and 14. The model group mice were fed for 12 weeks, and except for the day of LPS infusion, they were exposed to flue gas with a tar content of 10 mg / m³ daily. 3A COPD mouse model was obtained.

[0075] Specifically, the LPS solution infusion procedure includes the following steps:

[0076] S11: Mice in the model group anesthetized by intraperitoneal injection of 1% sodium pentobarbital, with an injection dose of 50 mg / kg. Figure 1A );

[0077] S12: The limbs and head of the model group mice were fixed to a mouse board to expose their pharyngeal airway. Figure 1B );

[0078] With the aid of a transilluminator, a flexible tube with a guidewire was inserted into the trachea, and LPS solution was slowly dripped into the model group mice. Figure 1C The injection dose is 7.5 μg / animal.

[0079] S13: Rotate and shake the model group mice to ensure that the drug is evenly delivered to all parts of the lungs. After the model group mice recover, they are fed under normal conditions.

[0080] Specifically, a smoke environment was created daily using the CS system to expose the model group mice to smoke for 12 weeks. No smoke exposure was administered on the days of intratracheal instillation of LPS solution (i.e., days 1 and 14). The CS system was used as follows: Figure 2 As shown.

[0081] The smoke exposure treatment procedure was as follows: The model group mice were exposed to mainstream cigarette smoke for 2 hours at a fixed time each day (e.g., 8:00 AM), and then the smoke exposure was stopped, and the model group mice were subjected to a smoke-free treatment for 4 hours. After the smoke-free treatment ended, the model group mice were exposed to mainstream cigarette smoke again for 2 hours.

[0082] Specifically, in the experiment to construct the mouse model, the average total particulate matter concentration of cigarette smoke exposed to the model group mice for the first two weeks was maintained at 40 mg / m³. 3 The concentration was maintained at 150 mg / m² from week 3 to the end of week 12. 3 Through the inventors' research, it was found that by dividing the model group mice into two stages and treating them with different total particulate matter concentrations, a buffer adaptation of the mice to flue gas in the early stage can be established, thereby improving the survival rate of the mouse model and enabling the mouse model to be constructed in a shorter time.

[0083] The specific parameter settings for the CS system are as follows: Figure 3 As shown, the parameters are set as follows:

[0084] Dilution flow rate: 10.00 L / min, suction flow rate: 9.00 L / min, differential pressure setting: 10.00 Pa, upper temperature limit: 25.00℃, lower temperature limit: 19.00℃, upper humidity limit: 70.00%RH, lower humidity limit: 30.00%RH, upper differential pressure limit: 50.00 Pa, lower differential pressure limit: 0.00 Pa, upper oxygen concentration limit: 25.00%, lower oxygen concentration limit: 19.00%, upper carbon dioxide concentration limit: 1.000%, lower carbon dioxide concentration limit: 0.000%.

[0085] Comparison Example

[0086] Adult C57 / BL-6 mice aged 6-8 weeks were used and housed in individual cages in an SPF-grade animal facility. The mice were allowed free movement, access to food and water, and were tagged and numbered as the control group, with 30 mice in each group. On days 1 and 14, 0.9% saline solution was administered intratracheally to the control mice at a dose of 7.5 μg per mouse.

[0087] To further illustrate the advantages of the present invention, the model mice used in constructing the mouse model of the present invention were subjected to the following tests one and two.

[0088] Test 1

[0089] After 4, 8, and 12 weeks of exposure to flue gas, some mice in the model group were removed, sacrificed, and lung tissue was collected. The lung tissue was fixed in 4% paraformaldehyde solution, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and the pathological changes of the lung tissue were observed under an optical microscope.

[0090] After 4, 8, and 12 weeks of normal feeding, some mice in the control group were removed, sacrificed, and lung tissue was collected. The lung tissue was fixed in 4% paraformaldehyde solution, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and the pathological changes of the lung tissue were observed under an optical microscope.

[0091] Test 2

[0092] After 4, 8, and 12 weeks of exposure to smoke, some mice in the model group were removed. The airway resistance (RI), peak expiratory flow (PEF), dynamic lung compliance (Cdyn), forced expiratory volume at 90 ms (FEV90), and forced expiratory volume (FVC) of each group of mice were measured using a small animal invasive pulmonary function instrument, and the FEV90 / FVC ratio was calculated.

[0093] After 4, 8, and 12 weeks of normal feeding, some mice in the control group were removed and their airway resistance (RI), peak expiratory flow (PEF), dynamic lung compliance (Cdyn), forced expiratory volume at 90 ms (FEV90), and forced expiratory volume (FVC) were measured using a small animal invasive pulmonary function instrument. FEV90 / FVC was then calculated.

[0094] HE staining results in Test 1 showed that, compared with the control group mice, after 4 weeks of LPS+CS system treatment, the model group mice exhibited alveolar cavity dilation, alveolar wall rupture, and fusion of adjacent dilated alveolar cavities into larger cysts. Inflammatory cell infiltration was observed in some lumens and alveoli. Figure 4A (4 weeks).

[0095] By week 8, the severity of the aforementioned pathological changes in the model group mice had increased. Figure 4B (8 weeks).

[0096] By week 12, HE staining results in the model group mice showed alveolar wall rupture, fusion of dilated alveolar cavities into large sacs, and significant inflammatory cell infiltration within the lumens and alveoli. Figure 4C (12 weeks).

[0097] Therefore, based on the above pathological results, it can be determined that by week 12, the lung tissue of the model group mice had developed relatively severe tissue damage, inflammatory infiltration, and emphysema, which is consistent with the pathological characteristics of COPD.

[0098] Test 2 showed that (Figure 5, 12 weeks) the invasive lung function index test results showed that, compared with the control group mice, the FEV90 / FVC and PEF of the model group mice at 12 weeks of modeling were significantly decreased, while RI was significantly increased, all of which were statistically significant (P < 0.05).

[0099] The combined morphological findings and changes in lung function suggest that the COPD animal model was successfully established in this study.

[0100] In summary, this invention establishes a method for constructing a COPD animal model using an LPS combined with a CS system. This method offers superior modeling time compared to previous composite modeling methods, with a high modeling success rate, high animal survival rate, clearly defined and controllable parameter mechanisms, and minimal experimental errors. Furthermore, this modeling method aligns with actual consumer behavior and the clinical pathogenesis of COPD, demonstrating significant application potential. Moreover, the established COPD animal model can replicate the progressive worsening characteristics of clinical disease, making it suitable as an experimental model for treatment and possessing broad application value.

[0101] The terminology and expressions used herein are for descriptive purposes only, and the invention should not be limited to these terms and expressions. The use of these terms and expressions does not imply the exclusion of any illustrative and descriptive equivalents (or parts thereof), and it should be recognized that various modifications that may exist should also be included within the scope of the claims. Other modifications, variations, and substitutions may also exist. Accordingly, the claims should be considered to cover all such equivalents.

[0102] Similarly, it should be noted that although the present invention has been described with reference to the specific embodiments described above, those skilled in the art should recognize that the above embodiments are only used to illustrate the present invention, and various equivalent changes or substitutions can be made without departing from the spirit of the present invention. Therefore, any changes or modifications to the above embodiments within the scope of the essential spirit of the present invention will fall within the scope of the claims of the present invention.

Claims

1. A method for constructing a COPD mouse model, characterized in that, Includes the following steps: Step S1: On day 1, LPS solution was instilled into the trachea of ​​the mice for the first time; Step S2: Starting one day after the first infusion of LPS solution, the mice were fed in the first stage of feeding, which lasted for 7 to 16 days, during which the mice were continuously exposed to the flue gas environment. Step S3: On the first day after the end of the first stage of feeding, LPS solution was administered to the trachea of ​​the mice for the second time. Step S4: Starting one day after the second infusion of LPS solution, the mice were fed in the second stage of feeding for 10 to 15 weeks, during which the mice were continuously exposed to the flue gas environment. Step S5: Obtain the COPD mouse model.

2. The method for constructing a COPD mouse model according to claim 1, characterized in that, The mice in question were adult mice aged 6-8 weeks from the C57 / BL-6 strain. In step S2, the continuous exposure of the mice to the smoke environment includes the following steps: Step S21: The mice were exposed to mainstream cigarette smoke at a fixed time in the morning for 1 to 3 hours. Step S22: The mice obtained in step S21 are subjected to smokeless treatment for 2 to 4 hours. Step S23: Expose the mice obtained in step S22 to the mainstream cigarette smoke environment again for 1 to 3 hours.

3. The method for constructing a COPD mouse model according to claim 2, characterized in that, During the first stage of feeding, the average total particulate matter concentration in the mainstream cigarette smoke environment was maintained at 30–50 mg / m³. 3 between, During the second stage of feeding, the average total particulate matter concentration in the mainstream cigarette smoke environment was maintained at 140–160 mg / m³. 3 between; The tar content in the mainstream cigarette smoke environment is 10 mg / m³. 3 .

4. The method for constructing a COPD mouse model according to claim 1, characterized in that, The first infusion of LPS solution includes the following steps: Step S11: Anesthetize the mice with sodium pentobarbital. Step S12: Expose the trachea of ​​the anesthetized mouse and slowly drip the LPS solution into the airway of the mouse through a soft tube with a guide wire, wherein the injection dose of the LPS solution is 6-8 μL / mouse; Step S13: Rotate and shake the mouse obtained in step S12 to allow the LPS solution to enter all parts of the lungs evenly.

5. The application of a flue gas system combined with lipopolysaccharide in establishing a COPD mouse model according to any one of claims 1-4.

6. The application according to claim 5, characterized in that, The flue gas system is the HRH-MNE3026 small animal single-concentration oral-nasal exposure system.

7. The application according to claim 6, characterized in that, The flue gas concentration in the flue gas system can be set. The exposure time of the mice to the mainstream cigarette smoke environment can be set by the smoke system.

8. The application according to claim 7, characterized in that, The parameters of the flue gas system include: an upper temperature limit of 25.00℃, a lower temperature limit of 19.00℃, an upper humidity limit of 70.00%RH, a lower humidity limit of 30.00%RH, an upper pressure limit of 50.00Pa, a lower pressure limit of 0.00Pa, an upper oxygen concentration limit of 25.00%, a lower oxygen concentration limit of 19.00%, an upper carbon dioxide concentration limit of 1.000%, and a lower carbon dioxide concentration limit of 0.000%.

9. The application according to claim 8, characterized in that, The dilution flow rate of the flue gas system is set to 5.00–15.00 L / min, the extraction flow rate is set to 5.00–10.00 L / min, and the pressure difference is set to 5.00–20.00 Pa.

10. A method for screening drugs for the treatment and / or prevention of COPD, characterized in that, The method includes the following steps: Step 1): The drug to be tested is administered to the mouse model constructed by the construction method according to any one of claims 1-4; Step 2): Analyze and evaluate the therapeutic effects of the test drugs, and select test drugs that can significantly improve the pathological characteristics of COPD in mouse models.

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