动物造模,药效评价,胆囊炎 z-bio 2024-09-02 607

　　(1) Method of replication: Guinea pigs, regardless of gender, weighing 300-400g, were intraperitoneally injected with lincomycin hydrochloride (LIN) at a dose of 60mg/kg body weight for 7 consecutive days; Alternatively, administer lithocholic acid (LCA) at a dose of 300mg/kg body weight once daily for 15 consecutive days; Alternatively, a dose of 200mg/kg body weight can be administered as a one-time intramuscular injection of a-naphthoxythiocyanate (ANIT). From 7 to 35 days after administration, blood samples are collected to prepare serum, the gallbladder is removed by laparotomy, weighed, and bile is extracted for biochemical analysis. The gallbladder contents are observed by naked eye and microscope, and the gallbladder tissue is examined for histomorphology and enzyme tissue chemistry using light microscopy and enzyme tissue chemistry techniques, respectively.

　　(2) The characteristics of the model are that both lincomycin and lithocholic acid can cause weight loss, increase gallbladder volume, and increase the number of stones formed in the gallbladder. Among them, in the early stage of the lincomycin model (experiment 7d), most animals were accompanied by hypersecretion of mucosal glands, edema in the submucosal and lamina propria layers, and excessive exudation of fibers. In the later stage (experiment 14-35d), gallbladder lesions were chronic proliferative inflammation, manifested by significant epithelial cell proliferation, increased mucosal folds and crypts sinking into the lamina propria layer, and mucosal sinking deep into the muscle

　　Layer formation of Rokitansky Ascaff sinus; The lithocholic acid model is characterized by hepatocyte degeneration and necrosis, decreased hepatocyte function, bile metabolism disorders, increased endogenous β - glucuronidase (β - GCD) activity, and increased Ca2+levels; The model of thiocyanate-a-naphthyl ester shows severe proliferation of mucosal epithelial cells, general increase in goblet cells, abundant mucosal folds and sunken crypts, proliferation of glandular tissue in the lamina propria, mostly in the form of acinar glands with lobular sinus formation.

　　(3) The etiology of human cholecystitis in comparative medicine is closely related not only to gallstones, but also to changes in bile composition, bile stasis, infection and immune dysfunction, and antibiotic allergy. Ordinary guinea pigs are allergic to antibiotics, and their normal gut microbiota can easily produce endotoxins when combined with antibiotics, which can cause cholecystitis in guinea pigs. As an antibiotic, lincomycin can cause a guinea pig cholecystitis model characterized by jaundice and elevated transaminase levels, accompanied by stones. The biggest drawback of this model is the high mortality rate. Cholic acid is one of the metabolic products of cholesterol in the body. Excessive lithocholic acid can cause damage to the liver, leading to metabolic disorders of cholesterol and bile acids. Repeated administration of large amounts of lithocholic acid can cause changes in total bilirubin, conjugated bilirubin, total cholesterol and other components in guinea pig bile, leading to a significant proliferation of bile duct cells and fibers, resulting in chronic proliferative cholecystitis. The model of thiocyanate-a-naphthyl ester cholecystitis belongs to the cholestatic type, manifested as acute proliferative cholecystitis.