动物造模,药效评价 z-bio 2024-08-21 372

　　(1) Method of replication: Adult rats were orally administered with 55 ℃ 15% sodium chloride (NaCl) solution or simply 10ml/kg body weight of 55 ℃ distilled water once daily for 12-32 weeks. During this period, the general activity of the animals was continuously observed. After the modeling was completed, the stomach was anesthetized and opened for general observation by cutting along the major bend, including the color, elasticity, number of folds, and richness of mucus of the mucosa. Samples were quickly taken along the minor bend, including the gastric antrum and some parts of the stomach body, and then histopathological examination was performed. The development of the criteria for chronic atrophic gastritis was based on the 1994 Houston Gastritis Diagnosis and Classification Standards and the 2000 Jinggangshan Gastritis Classification Standards in the United States. Microscopic instruments were used to measure mucosal thickness, glandular width, and cell thickness.

　　(2) Model features: After 2 weeks of gastric lavage with a 15% NaCl hot water solution, a small amount of eosinophils and lymphocytes began to infiltrate between the gastric mucosal muscle layer and the mucosal layer. At 4 weeks, the amount increased, and at 6 weeks, the mucosal gland narrowed, and the distance between the mucosal muscle layer and the gland widened. There was also a proliferation of lymphocytes and fibroblasts, and the proliferating fibroblasts were parallel to the mucosal gland, with a decrease in eosinophils. At 8 weeks, significant fibroblast proliferation was observed, and the smooth muscle of the mucosal muscle layer was inserted into the mucosal lamina propria in a spike like manner, with blood vessels dilated and congested. A small amount of lymphocytes and eosinophils could be seen infiltrating. At 10-12 weeks, the gastric mucosal gland significantly shrank, and the smooth muscle of the mucosal muscle layer showed bundle like proliferation and inserted into the mucosal lamina propria. The upper 1/3 to 2/3 of the gland were found Epithelial atrophy, widening of glandular lumen, and narrowing of mucosal width in the neck of the gastric pit. At this time, electron microscopy showed that the surface of the gastric mucosal cells in the model animal was rough, with ulcerated and flattened mucosal surfaces. At 32 weeks, the gastric mucosal cells atrophied, the glandular lumen diameter increased, the cell surface was stained, and there was fibrous exudation. After 24 weeks of simple hot water gavage, the gastric mucosal glands significantly shrank, and the upper 1/3 to 2/3 glandular epithelium atrophied, with a degree similar to the histopathological changes observed after 10-12 weeks of gavage with 15% NaCl hot water solution. The atrophy of the rat gastric mucosa became more pronounced at 32 weeks. Scanning electron microscopy showed that at 24 weeks, gastric mucosal cells atrophied, glandular cavities enlarged, and bleeding was observed; At 32 weeks, in addition to atrophy of gastric mucosal cells and more obvious enlargement of glandular cavities, a large number of epithelial cells shed, cells were damaged, and focal mucosal erosion was observed. Transmission electron microscopy showed that at 24 weeks, the gland atrophied, fibrous connective tissue proliferated and surrounded the gland, the glandular cavity was irregular, glandular cells atrophied, intercellular spacing increased, cytoplasmic organelles decreased, secretory granules decreased and vacuolized, rough endoplasmic reticulum significantly expanded, and a small number of cells showed a decrease in nuclear chromatin and an increase in heterochromatin near the nuclear membrane, indicating early apoptosis. At 32 weeks, cell atrophy became more pronounced, cytoplasmic organelles sharply decreased, and early apoptosis became more common.

　　(3) Chronic atrophic gastritis (CAG) in comparative medicine is a common disease of the digestive system. Its incidence rate is high, the course of disease is long, and the condition is complex. CAG plays an important role in precancerous lesions of gastric mucosa. Although the etiology and pathogenesis of CAG are still not fully understood, the multiple occurrences and long-term chronic irritation of acute gastritis are undoubtedly closely related to its occurrence and development. Experiments have shown that long-term stimulation with hot water can also damage the gastric mucosa and cause inflammatory reactions; High salt can stimulate the gastric mucosa, leading to the shedding of parietal cells, thereby damaging the gastric mucosal barrier and causing atrophic gastritis; The combination of hot water and high salt content exacerbates the degree of gastric mucosal damage and accelerates the rate of intrinsic glandular atrophy. The biggest feature of this model is that the selection of modeling factors is relatively close to human dietary habits, with advantages such as short modeling cycle, simple method, high modeling rate, and good reproducibility. It also has pathological features such as shrinking of mucosal intrinsic glands, atrophy of glandular epithelium, infiltration of lymphocytes and eosinophils in the intrinsic layer, but it is difficult to see pathological phenomena such as intestinal glandular metaplasia and pseudo pyloric glandular metaplasia. This model is suitable for studying the correlation between dietary habits and the occurrence, development, and carcinogenesis of chronic atrophic gastritis.