动物造模,药效评价 z-bio 2024-08-02 467

　　In 1975, Lomobardi et al. established a female mouse model of acute hemorrhagic necrotizing pancreatitis by feeding a choline deficient diet supplemented with ethionine. Choline is a member of the vitamin B complex and a component of the cell membrane. Ethylene methionine is a derivative of methionine. The pathogenic mechanism of this model may be due to choline deficiency and interference from ethionine, which hinder the synthesis of cell membrane phospholipids and hinder the extracellular release of acinar cells. This results in the co localization of lysosomes and exocrine vesicles, leading to the activation of digestive enzymes and self digestion in acinar cells similar to rain frog hormones, resulting in the onset of the disease. Estrogen plays an important role in it, so female mice are generally selected as model animals for this model, or male mice are injected with estrogen.

　　【 Modeling Method 】 4-6 week old female mice were fed CDE feed: 55% sucrose, 20% lard, 10% soy protein, supplemented with various vitamins and inorganic salts, and 0.5% ethionine water. After fasting for 12-24 hours, mice were fed 3g/d CDE feed, and the mortality rate was almost 100% within 5 days. Under non fasting conditions, reducing the amount of CDE feed can alleviate the pathological degree of pancreatitis. The induction time can be extended to 24 weeks or even longer by separating CDE feed from regular feed. CDE feed can also be used to induce chronic pancreatitis. Rats are also used in this model.

　　The CDE method can create pancreatitis models of different degrees in a gradient manner. By changing the feeding time, method, and concentration of methionine in the CDE diet, different severity and mortality rates of pancreatitis can be caused. CDE method can cause severe hemorrhagic necrotizing acute pancreatitis, accompanied by liver damage and other symptoms such as ascites, hypoxia, hypovolemia, and acidosis. During the modeling process, it is necessary to strictly monitor the feeding amount and status of mice, individual differences, and comparability between the experimental group and the control group.

　　[Model Evaluation and Application] This model is simple and easy to implement, with good repeatability, and can control the severity, pathological and biochemical characteristics, and multi organ damage of pancreatitis. It is very similar to human diseases and is suitable for research on etiology, pathology, and diagnosis. The potential effects of experimental treatment methods can be determined by measuring survival rates, biochemical characteristics, histopathology, hematocrit, and blood gas analysis, and the changes in these physiological indicators largely simulate the situation of human diseases. The main limitations of this model are: high feed costs; Suitable for animals that are too young in age; CDE feed has no specific toxic effect on the pancreas; Each experiment requires careful monitoring of animal feeding and status; Each experiment requires on-site adjustment of the experimental plan.