动物造模,药效评价,肺心病 z-bio 2024-06-19 390

　　1. Animal modeling materials: rats; Medication: 2% monocrotaline (MCT) aqueous solution (400mg monocrotaline, dissolved in 2.4ml 1mol/L hydrochloric acid, diluted to 5-6ml with double distilled water, then neutralized with 0.5mol/L sodium hydroxide, and water added to 20ml to form a 2% aqueous solution).

　　2. Method of modeling: The animals in the 60mg/kg modeling group were injected subcutaneously under the scapula, or injected intraperitoneally with a 60mg/kg solution of wild lily alkaloids.

　　3. Modeling principle: Wild lily alkaloids cause pulmonary heart disease in animals.

　　4. Changes after modeling: The control group animals had shiny, dense, and tightly fitting fur, normal appetite, lively and bright eyes, active movements, and a responsive response. Their bowel movements were normal. The model group animals have poor mental health, slow movements, lack of concentration in their eyes, sparse fur, fear of the cold, and curl up in a corner.

　　After 13 days of modeling, animals developed pulmonary heart disease, with a 54% increase in pulmonary heart weight compared to normal. Compared with the control group [(1.45 ± 0.33) kPa], the pulmonary artery pressure in the modeling group [(2.08 ± 0.51) kPa] was significantly increased, and the blood ET level was significantly increased [modeling group was (904.48 ± 231.41) pg/ml, control group was (519.61 ± 139.52) pg/ml]. The NO level was significantly reduced [modeling group was (32.38 ± 11.33) 1 μ mol/ml, control group was (66.31 ± 19.93) μ mol/ml].

　　Under the light microscope, observe the pulmonary artery blood vessels of the normal control group. The endothelial cells are flat and continuous, with uniform cell distribution and consistent size and thickness. Under electron microscopy, normal pulmonary artery endothelial cells are flat and tightly adhere to the basement membrane, with microvilli appearing on the free surface of the cells. One week after injection of MCT, pulmonary artery endothelial cells swell, microvilli disappear, cells protrude into the vascular lumen, and mitochondria and endoplasmic reticulum swell significantly; The basal protrusions of degenerated pulmonary artery endothelial cells increase, and there is an increased connection between them and smooth muscle cells that migrate into the subintima. Three weeks after injection of MCT, there was significant damage to the endothelial cells of the pulmonary artery, with necrosis and shedding. Platelets adhered to the damaged endothelial cells and exposed basement membrane, forming platelet thrombosis; Fibroblast proliferation can be seen in the blood vessel wall of the alveolar septa.

　　The results of paraffin sectioning and light microscopy observation showed that MET induced significant enhancement of pulmonary artery muscle formation, which became increasingly severe over time, with the most severe muscle formation occurring in the intra acinar arteries. In the second week of MCT injection, the proportion of arterial media thickness was more than twice that of the normal control group, and by the third week, the proportion of acinar artery media thickness reached more than half of the pulmonary artery diameter. However, the larger diameter pulmonary artery did not show a significant increase in the proportion of arterial media thickness until the second week. The degree of pulmonary artery calcification is closely related to the degree of right heart hypertrophy; The proportion of intimal thickness in intramuscular and acinar arteries in the lungs significantly increased, with more pronounced changes in the acinar arteries; The right heart hypertrophy index significantly increased.