[Animal Modeling]-Cysteamine-induced duodenal ulcer animal model

  (1) Feeding method Adult rats fasted for 24 hours, after subcutaneously administering 400 mg/kg body weight or 300 mg/kg body weight of hydrochloric acid amine hydrochloride, the same route was used to administer body weight at a dose of 100 mg/kg. 6 hours apart. once. 24 hours after the first administration, the animals were sacrificed by cervical dislocation. Take the proximal end of the stomach and duodenum (about 5 cm below the pylorus), and cut the specimen along the opposite side of the larger curvature of the stomach and mesentery. Observe the duodenum. Intestinal injury is calculated as the ulcer index. At the same time, the pH of the contents of the stomach and duodenum, the amount of mucus bound to the duodenal wall, the rate of DNA synthesis in the duodenal tissue, and the morphology of the duodenal tissue are measured. Learn to change. The ulcer index is calculated by the cumulative ulcer depth index score and the surface damage index score. The scoring criteria for the depth index are: no damage: 0 points; mucosal necrosis: 1 point; ulcer reaching the muscle layer: 2 points; almost or only penetrating the serosal membrane: 3 points; perforation and adhesion to liver, pancreas or intestinal contents Leakage of neighboring tissues: 4 points. The scoring standard of the surface damage index is as follows: the length of the damaged surface is 5 mm: 2 points, and the damaged surface occupies more than half of the entire specimen area: 3 points.

  (2) Model characteristics: subcutaneous injection of cysteamine hydrochloride 400mg/kg body weight, the duodenum of model animals mainly manifests mucosal erosion and ulcers, the surface of the ulcers is large, and the diameter reaches 2-8mm. The depth reaches the mucosal layer or submucosa, the duodenal gland disappears, granules are formed in the ulcer, and epithelial cells are lost or degenerated. The duodenum of model animals was injected subcutaneously with 300 mg of Systemamin hydrochloride and 100 mg/kg body weight twice every 6 hours, indicating that the ulcer had spread to adjacent organs (liver, spleen, uterus, etc.). The ulcer reaches the deep muscle or outer membrane and may be accompanied by perforation, duodenal necrosis, loss of epithelial cells, and formation of granulation tissue. After 50 days of modeling, these symptoms did not improve significantly.

  (3) Two important factors that cause duodenal ulcers in comparative medicine are hypersecretion of gastric acid and impaired mucosal barrier. Under physiological conditions, the alkaline fluid in the duodenal cavity can neutralize gastric acid, and the combined mucus secreted by the duodenum adheres to the surface of the intestinal mucosa in a stable, continuous gel state, and is secreted by the mucosa. . Mucus-HCO3-barrier has a specific protective effect on the duodenum. Under pathological conditions, such as excessive gastric acid secretion, insufficient duodenal secretion or rapid bowel movement, alkaline fluid cannot reach the proximal end of the duodenum to neutralize acid and duodenum, which may lead to its acidification. When the erosion of excessive gastric acid and pepsin is out of balance with the protective function of the duodenal mucosa, duodenal ulcers will form. Cysteamine (cysteamine, CS), also known as β-mercaptoethylamine, is a component of coenzyme A. Because of its active sulfhydryl and amino groups, it has a variety of biological functions. When an excessive amount of systemic amine is injected into an animal's body, it will reduce the ability of the duodenum to process acid, inhibit the activities of acid anhydrase carbonate, ATPase and alkaline phosphatase, and impair the function of the mucous secreting glands. The content of mucus and mucus glycoprotein in the glands weakens the barrier function of duodenal mucus-HC03 and leads to the development of ulcers. The type and pathological changes of duodenal ulcer in animals caused by cysteamine are largely related to the dosage and method of cysteamine injection. After subcutaneous injection of cysteamine hydrochloride 400 mg/kg body weight, the model animals showed acute non-diffuse duodenal ulcer. Cysteamine hydrochloride 300 and 100 mg/kg body weight were injected subcutaneously twice at 6-hour intervals. Model animals showed chronic diffuse duodenal ulcer. The pathological characteristics of this model are very similar to human clinical manifestations. The method is simple and easy to implement, making it one of the most commonly used duodenal ulcer models.