动物造模,药效评价,胃炎 z-bio 2024-08-26 440

　　(1) Method of replication: Adult rats were fasted without water for 18 hours, and then anesthetized with pentobarbital sodium at a dose of 30mg/kg body weight. The stomach and jejunum were exposed, and the anterior stomach about 2cm away from the pylorus and the jejunum 5-7cm away from the pylorus were fixed together. Firstly, make an incision of 0.5-0.7cm in the anterior stomach, carefully rinse the stomach cavity with physiological saline, and then make an equally large incision in the corresponding small intestine area. Suture the inner and outer sides of the stomach and small intestine incision in sequence. After sealing the incision, rinse the abdominal cavity twice with physiological saline, dry it with disinfectant gauze, and inject 2-3 drops of gentamicin diluent. Suture the muscle layer and skin layer by layer, close the abdominal cavity and add 2-3 drops of gentamicin dilution solution, fast for 24 hours, and then feed regularly. After 9-13 weeks of surgery, fasting for 24 hours, anesthesia and laparotomy were performed. The pylorus, cardia, and both sides of the anastomotic site were ligated, and 15 minutes later, the stomach was cut along the greater curvature to collect gastric juice. The total amount of bile acid in the stomach was measured, and its pH value was recorded. Observe the pathological changes of the gastric mucosa with the naked eye, and take samples from the bottom of the stomach, antrum, greater curvature of the stomach, lesser curvature of the stomach, and around the gastro intestinal anastomosis for light and electron microscopy examination. Or adult dogs, under anesthesia, open the abdomen, ligate the common bile duct, and perform anastomosis between the bottom of the gallbladder and the anterior wall of the stomach (bile reflux model), or anastomosis between the jejunum and the anterior wall of the stomach (biliary pancreatic reflux model). During the operation, one piece of gastric antrum and one piece of gastric body mucosal tissue were respectively cut as controls before modeling. At 6 months after surgery, the gastric mucosa was observed by gastroscopy, and under direct visualization, a curved side was taken at a distance of 2.5-3.0cm from the pylorus. A piece of gastric antrum and gastric body mucosal tissue were also taken for light and electron microscopy examination.

　　(2) Model features: The pH value in the stomach of the model rats increases, the content of bile acid increases, and most of the gastric juice appears yellow green. The surface of the gastric mucosa is covered with thick white membrane like substances, most of which are yellow stained. The gastric mucosa is congested or congested, with obvious edema. Edema is prominent in the anterior stomach around the anastomotic site, arranged in a pebble shape; The mucosal folds of the gastric body decrease or even disappear, and the tension of the gastric wall is significantly reduced; The gastric mucosal tissue shows obvious infiltration of inflammatory cells, mostly occurring in the submucosal lamina propria, and some can extend to the mucosal muscle layer and submucosal layer. The inflammatory cells are lymphocytes, neutrophils, and a small number of eosinophils. Atypical glandular hyperplasia or atrophy, gastric pit dilation, and intestinal metaplasia can still be seen in the mucosal tissue around the anastomotic site. The model dog also showed significant infiltration of gastric mucosal inflammatory cells, glandular atrophy, and intestinal metaplasia. Inflammatory cells are mainly neutrophils and lymphocytes, and infiltration often occurs in the gastric mucosal glands and submucosa. In the bile reflux model of dogs, there is proliferation of gastric mucosal epithelial cells, partial necrosis and shedding, significant deformation of the gastric pit opening, deepening and enlargement of the gastric pit, and even expansion into a fissured shape. The hyperplasia of gastric antral mucosal epithelium is similar to that of small intestine epithelium, with surface microvilli growing. The canine model of bile pancreatic reflux shows more severe damage to the gastric mucosa, with large areas of epithelial cells necrotic and shedding, forming ulcer surfaces covered by necrotic material. The mucosal surface structure is unclear, and as inflammation heals, some glandular atrophy or hyperplasia may occur. In severe atrophic gastritis, the gastric pits and their connections completely disappear, and the mucosa becomes flat.

      (3) In clinical comparative medicine, dysfunction of the pyloric sphincter or gastrojejunostomy often causes intestinal reflux. Bile and pancreatic juice reflux into the stomach, increasing the pH value of gastric juice, altering the composition and structure of mucus, and reducing its barrier function; At the same time, certain components in the contents of the duodenum, such as bile acids and lysophosphatidylcholine, have a descaling effect, causing damage to the lipid membrane of mucosal cells, increasing the permeability of the cell membrane, and promoting the diffusion of H+and pepsin into the mucosa, leading to mucosal damage; Bile entering the stomach stimulates an increase in gastric acid secretion. Bile salts bind with gastric acid, increasing the activity of acidic hydrolytic enzymes, damaging lysosomal membranes, leading to cell fragmentation and ulcers; The hemolytic phospholipids in bile can cause further damage to the gastric mucosal barrier through the action of phospholipase A in pancreatic juice. Under the long-term stimulation of the above factors, gastric tissue gradually evolves into the same pathological process, namely gastric mucosal inflammatory cell infiltration, glandular hyperplasia or atrophy, and intestinal epithelial metaplasia. This model simulates the pathological changes of chronic gastritis by performing gastro intestinal anastomosis, which causes the reflux of alkaline intestinal fluid into the stomach, resulting in a large number of inflammatory cell infiltration, and conforms to the characteristics of pathological structural changes of chronic atrophic gastritis. This model also shows that bile or bile pancreatic juice entering the stomach can cause severe damage to the gastric mucosa, but the latter is more severe, indicating that bile and pancreatic juice have a synergistic effect on the damage to the gastric mucosa. This model, due to its simple production method and clear pathological evolution process, is more suitable for the study of the etiology and mechanism of intestinal reflux in chronic atrophic gastritis and the observation of drug efficacy.