动物模型,慢性萎缩性胃炎 z-bo 2020-08-07 510

　　(1) Reproduction method 5-6 week old rats, put 0.05% methylnitronitrosoguanidine (MNNG) into a drinking bottle for drinking, the daily drinking amount is 50ml/mouse, for 1 month; Or put 0.01-O.02% ammonia water into a drinking bottle for free drinking for 3-6 months. Or 7-week-old male rats were given 0.05% indomethacin by gavage, 1 time/d, 8ml/(kg·times), or 60% ethanol by gavage on an empty stomach, 2 times/week, 8ml/(kg·times) At the same time, 20mmol/L sodium deoxycholate was given by intragastric administration, 1 time/d, 8ml/(kg·time), both for 6 months. Or 7 to 8 weeks old rats, gavage 2% sodium salicylate solution, 1 time/d, 2ml/time, for 6 weeks, fasting for 1h before and after gavage, and free eating and drinking for the first 3 weeks Water; for the next 3 weeks, one day fasting and free drinking, two days with adequate food and free drinking, and swimming in warm water every other day, 10min/time. Throughout the modeling process, continuously observe the animal's mental state, activity, hair gloss, appetite and urine and feces, and record the weight change. After modeling, anesthetize the abdomen and remove the stomach, and cut it along the large curve for general observation , Including the color, elasticity, number of folds of the mucous membrane, and whether the mucus is abundant, quickly take the material along the small curvature, including the antrum and part of the stomach, and then do histopathological examination.

　　(2) Characteristics of the model The model animals are depressed, with reduced activity, rough and dull coat, and slow weight gain. The surface of the gastric mucosa is rough and dry, with little mucus, a little or flaky bleeding, flat or disappearing gastric folds, dark color of the mucosa, and poor elasticity. MNNG model animal gastric tissue mucosal erosion, gland atrophy, hyperplasia, necrosis, mucosal layer and submucosa inflammatory cell infiltration. Three months after the modeling of the ammonia water model animals, the glands of the gastric body shrank, the number of mucosal wall cells decreased, the pH value of the mucosal surface increased, and PAS positive substances (the mucogen particles in the epithelial cells that can be colored by PAS staining and the mucosa covered The mucous membrane on the surface) decreased. This change was more obvious at 6 months after modeling, and it was positively correlated with the concentration of ammonia. In the indomethacin model and ethanol plus sodium deoxycholate model animals, the proper glandular layer of the gastric antrum becomes thinner at 6 months, the number of proper glands decreases, and the ratio of the section area occupied by the glands decreases, showing typical Atrophic gastritis of gastric antrum has a model rate of 100%. Sodium salicylate model gastric mucosal folds are irregular, surface mucous cell interstitial expansion, edema, lamina propria hyperplasia, infiltration of eosinophils and lymphocytes, and focal small intestinal metaplasia in the pyloric gland area.

　　(3) Comparative medicine Under physiological conditions, the gastric mucosa can produce mucus and HCO3-, and a pH gradient can be generated between the gastric cavity (low pH) and the replicating membrane (high pH) of an animal model of chronic atrophic gastritis. It becomes a barrier to the diffusion of gastric acid and pepsin; mucosal epithelial cells can remove excessive H+ through the membrane transport system, and can also prevent the reverse diffusion of H+ through tight joints; mucosal blood flow can remove excessive acid that diffuses to the epithelial layer. When the ammonia concentration or indomethacin content in the gastric juice reaches or exceeds a certain level, the epithelial cells on the gastric surface and the endogenous prostaglandin (PG) produced by them can be reduced, thereby weakening the gastric mucosa of PG and making the gastric mucosa The "mucus-bicarbonate" barrier is damaged, causing H+ reverse diffusion and destroying the integrity of epithelial cells. Long-term stimulation can cause chronic inflammation of the gastric mucosa. In addition to the above mechanisms, the damage of sodium salicylate to the gastric mucosa is also manifested in the direct stimulation of the local gastric mucosa, causing gastric mucosal inflammatory reaction, gastric mucosal cells peeling, and inhibiting the growth of gastric mucosa to make it lose its normal resistance. In addition, high concentrations of ethanol can directly damage the gastric mucosa; gavage sodium deoxycholate 20mmol/L to simulate duodenal bile reflux; MNNG with strong mutagenic ability can easily penetrate into the gastric pylorus and fundus mucosa. Chronic atrophic gastritis induced by long-term drinking has obvious pathological features such as gastric mucosal erosion, gland atrophy, gastric mucosal intestinal metaplasia and dysplasia, which are similar to clinical ones. The animal model of chronic atrophic gastritis induced by the above-mentioned chemical drugs or poisons, due to its single modeling factor and simple operation, has a high success rate, good stability, and low price. It is more suitable for preliminary evaluation of the efficacy of drug intervention .