动物造模,效评价,慢性阻塞性肺疾病 z-bio 2024-08-01 410

　　Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by airflow limitation, with inflammation as the core. It is related to abnormal inflammatory responses of the lungs to harmful gases or particles such as cigarette smoke (especially smoking), including chronic bronchitis and/or emphysema with airflow obstruction.

　　Smoking is the main pathogenic factor of COPD in humans. Harmful components in cigarettes can attack the airway epithelium, directly weaken the purification and defense functions of the respiratory tract, increase the burden of total inhaled particles and smoke in the lungs, cause airway inflammation and secondary emphysema, and also exacerbate respiratory symptoms and promote the occurrence of COPD. Therefore, the changes formed by the COPD animal model established by passive smoking are currently the closest to human COPD among all models.

　　【 Mold making method 】 Prepare an organic glass smoking box (20cm × 25cm × 30cm), with a ventilation hole with a diameter of 0.5cm left at the lower end of one side of the smoking box, and connected to a stainless steel smoke chamber on the opposite side (through). The smoke chamber inlet is connected to a small electric fan, and cigarette smoke enters the smoking box under the push of the fan's wind power, so that the smoke is evenly distributed inside the box and there is sufficient oxygen inside the smoke box. Smoking group rats were exposed to passive smoking once a day in the morning and afternoon. Three smoking group rats were placed in each smoking box, and three commercially available unfiltered Shuangxi brand cigarettes (containing approximately 25mg tar and 1.4mg nicotine in the smoke) were lit each time. Fresh cigarette smoke was continuously inhaled for one hour each time.

　　[Model features] The smoke induced group of rats showed characteristic pathological changes in the trachea, bronchi, and lung tissues of chronic bronchitis and obstructive emphysema. The overall presentation was partial detachment of ciliated epithelium, thickening of bronchial epithelium and fibroblasts, proliferation of mucinous glands and goblet cells, accumulation of mucus in the lumen, and infiltration of inflammatory cells mainly consisting of macrophages and lymphocytes in the airway wall and alveolar area around small blood vessels. After 10 weeks of smoking, there were abnormalities in the ciliated epithelium accompanied by high secretion of mucus; After 12 weeks of smoking, partial peeling of the ciliated epithelium in the airway can be observed; After 12-24 weeks of smoking, some alveolar fusion can be seen to form pulmonary bullae. The above pathological changes are more obvious after 24-36 weeks of smoking, especially after 36 weeks of smoking, the alveolar cavity is significantly enlarged, the airway wall is significantly thickened and fibrotic, and a large number of inflammatory cells can be seen infiltrating.

　　[Model Evaluation and Application] A rat COPD model was prepared by smoking cigarettes for 36 weeks, and the established rat COPD model conforms to the characteristics of human COPD. Multiple inflammatory cells are involved in the occurrence and development of COPD. The inflammatory cells in the airway cavity are mainly neutrophils, macrophages, and lymphocytes, while the lung parenchyma is mainly infiltrated by macrophages (CD68+) and T lymphocytes, especially CD3+and CD8+cells. IL-2、 IL-4、IL-6、IL-10、IL-13、IL-18、IFN-γ、 Monocyte chemoattractant protein (McP-1) and endothelin (ET) -1 play important roles in COPD airway inflammation. The high secretion of airway mucus, increased inflammatory cells, thickening of airway walls, and excessive deposition of extracellular matrix mainly composed of collagen are important pathological changes in COPD airway remodeling and the main causes of obstructive ventilation dysfunction. The Airway Resistance and Lung Compliance RC System (BUXCO) was used to detect airway resistance and lung compliance in rats. This model is mainly used for the study of COPD pathology, pathophysiological changes, and drug treatment.