动物造模,药效评价,慢性阻塞性肺疾病 z-bio 2024-07-31 446

　　Method 1

　　1. Modeling material animals: Clean grade Wistar rats, weighing 185-220g, male or female not limited; Drug: Klebsiella pneumoniae (6 ± 10 ^ 8 CFU/ml).

　　2. Modeling method: The control group was injected with 0.1ml of conventional bacterial culture medium through the nasal cavity twice a week for 2 months. Inject 0.1ml of Klebsiella pneumoniae solution into the nasal cavity twice a week for 2 months to create a model. The specific method of injecting through the nasal cavity is to use a disinfected 1ml syringe (connected to a 5.5mm injection needle, with the needle tip tightly wrapped in a plastic hose) to draw 0.1ml of culture medium or bacterial liquid, insert the needle tip into the nasal cavity of the rat, and inject the liquid while the rat is inhaling.

　　3. Modeling principle: Bacterial infection can cause chronic obstructive pulmonary disease in animals.

　　4. Changes after modeling: The cilia on the surface of the trachea and bronchi in the control group were arranged neatly without shedding. From the first week of modeling, the cilia of the trachea and bronchi adhered and collapsed, with some shedding. As the infection time prolonged, the shedding of cilia became more pronounced.

　　In the control group, there was no degeneration of bronchial epithelial cells, no exudate in the alveolar cavity, and no thickening of the alveolar septum. On the first day of modeling, there was a small amount of neutrophil infiltration in the walls of the bronchioles. Neutrophils and a small amount of red blood cells can be seen exuding from the alveoli in a local area. In the first and second weeks, there is a small amount of mucus, lymphocytes, and macrophages in the lumen of the bronchioles; The cilia on the surface of bronchial epithelial cells are still intact, but the intercellular spaces have widened; Wall inflammation gradually spreads and spreads to the surrounding area, with inflammatory cells mainly consisting of lymphocytes, plasma cells, and macrophages. Occasional exudation of lymphocytes, plasma cells, and macrophages is observed in some alveoli. In the fourth week, the number of bronchioles per unit area decreased, and respiratory bronchiolar lumen stenosis and occlusion increased relatively; The epithelial cells of the bronchioles are severely damaged, and goblet cells proliferate. There is a significant increase in lymphocyte and macrophage infiltration in the wall of the tube, and a small number of Klebsiella pneumoniae can be seen in the alveolar cavity. There is significant inflammation in the alveolar septum and alveolar cavity near the bronchioles, with increased infiltration of lymphocytes, plasma cells, and macrophages in the alveolar septum. Localized destruction of the alveolar septum is also common in this area, and multiple alveoli fuse with each other to form emphysema. In the 8th week, a small number of smooth muscle cells and fibrous tissue in the walls of bronchioles showed significant proliferation. In the 16th week, mucus formation was observed in some respiratory bronchioles, with significant proliferation of smooth muscle cells and fibrous tissue in the walls of the bronchioles. Pulmonary interstitial fibrosis was also more pronounced.

　　In the early stage of modeling, edema occurs around the pulmonary arterioles, gradually leading to infiltration of lymphocytes and plasma cells. Starting from the fourth week, the walls of small arteries become significantly thickened, and endothelial cells and smooth muscle cells proliferate.

　　From the 4th to the 16th week of modeling infection, the walls of the bronchioles in rats showed significant thickening, and the thickening became more pronounced over time. In the first week of modeling, the lumen of the rat bronchioles began to narrow, and from the fourth week onwards, the degree of stenosis worsened.

　　From the 16th week of infection, the arterial oxygen partial pressure PaO2 [9.18 ± 0.93 kPa in the modeling group, 12.37 ± 2.79 kPa in the control group] significantly decreased, while the blood carbon dioxide partial pressure PaCO2 [8.55 ± 0.33 kPa in the modeling group, 4.39 ± 0.80 kPa in the control group] significantly increased.

　　From the fourth week onwards, the right ventricular systolic pressure (RVSP) of the model group rats significantly increased, with the model group reaching (4.24 ± 0.40) kPa and the control group reaching (2.30 ± 0.25) kPa.

　　At the 16th week of modeling, the right ventricular hypertrophy index (RVHI) significantly increased to 0.48 ± 0.07, compared to 0.28 ± 0.02 in the control group.

　　Method 2

　　1. Modeling material animals: Clean grade Wistar rats, weighing 185-220g, male or female not limited; Drug: Streptococcus pneumoniae (6 × 10 ^ 8 CFU/ml).

　　2. Modeling method: The control group was injected with 0.1ml of conventional bacterial culture medium through the nasal cavity twice a week for 2 months. Inject 0.1ml of Streptococcus pneumoniae solution into the nasal cavity twice a week for 2 months to create a model. The specific method of injecting through the nasal cavity is to use a disinfected 1ml syringe (connected to a 5.5mm injection needle, with the needle tip tightly wrapped in a plastic hose) to draw 0.1ml of culture medium or bacterial liquid, insert the needle tip into the nasal cavity of the rat, and inject the liquid while the rat is inhaling.

　　3. Modeling principle: Bacterial infection can cause chronic obstructive pulmonary disease in animals.

　　4. Changes after modeling: The cilia on the surface of the trachea and bronchi in the control group were arranged neatly without shedding. From the first week of modeling, the cilia of the trachea and bronchi adhered and collapsed, with some shedding. As the infection time prolonged, the shedding of cilia became more pronounced.

　　In the control group, there was no degeneration of bronchial epithelial cells, no exudate in the alveolar cavity, and no thickening of the alveolar septum. On the first day of modeling, there was a small amount of neutrophil infiltration in the walls of the bronchioles. Neutrophils and a small amount of red blood cells can be seen exuding from the alveoli in a local area. In the first and second weeks, there is a small amount of mucus, lymphocytes, and macrophages in the lumen of the bronchioles; The cilia on the surface of bronchial epithelial cells are still intact, but the intercellular spaces have widened; Wall inflammation gradually spreads and spreads to the surrounding area, with inflammatory cells mainly consisting of lymphocytes, plasma cells, and macrophages. Occasional exudation of lymphocytes, plasma cells, and macrophages is observed in some alveoli. In the fourth week, the number of bronchioles per unit area decreased, and respiratory bronchiolar lumen stenosis and occlusion increased relatively. There is a significant increase in lymphocyte and macrophage infiltration in the wall of the tube, and a small number of Klebsiella pneumoniae can be seen in the alveolar cavity. There is significant inflammation in the alveolar septum and alveolar cavity near the bronchioles, with increased infiltration of lymphocytes, plasma cells, and macrophages in the alveolar septum. Localized destruction of the alveolar septum is also common in this area, and multiple alveoli fuse with each other to form emphysema. In the 8th week, a small number of smooth muscle cells and fibrous tissue in the walls of bronchioles showed significant proliferation. In the 16th week, mucus formation was observed in some respiratory bronchioles, with significant proliferation of smooth muscle cells and fibrous tissue in the walls of the bronchioles. Pulmonary interstitial fibrosis was also more pronounced.

　　In the early stage of modeling, edema occurs around the pulmonary arterioles, gradually leading to infiltration of lymphocytes and plasma cells. Starting from the fourth week, the walls of small arteries become significantly thickened, and endothelial cells and smooth muscle cells proliferate.

　　In the fourth week of modeling infection, the thickening of the walls of the bronchioles in rats was most significant, and then slightly slowed down. In the first week of modeling, the lumen of the rat bronchioles began to narrow, and from the fourth week onwards, the degree of stenosis worsened.

　　From the modeling stage to the 16th week of infection, PaO2 [modeling stage (9.98 ± 1.99) kPa, control group (12.37 ± 2.79) kPa] decreased, while PaCO2 [modeling stage (6.44 ± 3.66) kPa, control group (4.39 ± 0.80) kPa] increased.

　　From the fourth week onwards, the RVSP of the model group rats significantly increased, with the model group being (4.18 ± 0.60) kPa and the control group being (2.30 ± 0.25) kPa.

　　At the 16th week of modeling, RVHI significantly increased to 0.43 ± 0.07, compared to 0.28 ± 0.02 in the control group.