动物模型,急性胰腺炎 z-bo 2020-08-13 540

　　Animal models of pancreatitis are the best way to study the pathogenesis of pancreatitis and explore clinical treatment. However, due to the different pathogenesis of different types of pancreatitis, the pathogenesis of pancreatitis is still unclear, so there is no good method. Animal models can simulate human pancreatitis. However, since Busnar-do et al. injected a mixture of bile and olive oil into the canine pancreatic duct in 1856 and successfully induced an acute pancreatitis model, after more than a century of discussion, the preparation methods of pancreatitis animal models mainly include the following:

　　1. Sodium taurocholate modeling

　　1) Model establishment method: The rats were fasted 12h before surgery, freely drinking water, pentobarbital solution 2mg/100g body weight was intraperitoneally anesthetized and fixed. Enter the abdomen through a midline incision in the upper abdomen, lift the duodenum and clamp the duodenal segment and the hilar pancreaticobiliary duct with small vascular clips. Puncture the pancreaticobiliary duct with a TB needle (4.5 needle, 1ml syringe) (preferably with a micropump injection), and inject 5% C sodium taurocholate (0.1ml/100g) for 1 min, stay for 5 min, then pull out the needle and remove the vascular clamp . Observe obvious edema and hemorrhage in rat pancreatic tissue, suture all layers of abdominal wall.

　　2) Features and functions of the model: This method is a more mature model of acute necrotizing pancreatitis (ANP).

　　3) Precautions for model establishment and use: 24h survival rate is about 50%

　　2. Bombesin modeling

　　1) Model establishment method: The rats were fasted for 12 hours before the operation, free to drink, and bombesin (25μg/kg) was injected intraperitoneally, and 5 hours after injection, edematous acute pancreatitis (CIP) was formed

　　2) Features and functions of the model: This method is a model of edematous acute pancreatitis with a mild degree.

　　3) Precautions for model establishment and use: At present, ANP is mainly studied in China. Please pay attention to the research content when using this model.

　　3. Retrograde bile duct injection

　　Ligate the pancreaticobiliary duct, line the main pancreatic duct cannula, and inject substances or pancreatin that can activate pancreatin through the main pancreatic duct, such as sodium deoxycholate, autologous bile, etc. Pancreatin is injected into the pancreatic duct to produce acute pancreatitis, if it is infused with PGE2 at the same time, acute necrotizing pancreatitis will occur. Schmidt et al. used low-volume pancreatic duct infusion of glycodeoxycholic acid combined with intravenous injection of bombesin to make a rat model of acute pancreatitis, which can produce uniform damage of moderate necrosis of adenocytes, which is suitable for the study of pancreatitis.

　　4. Pancreaticobiliary ligation

　　was ligated into the duodenum pancreaticobiliary duct or simply ligated the pancreatic duct. Lerch et al. ligated the pancreaticobiliary duct in the ampulla. 6 hours after the ligation, edematous pancreatitis appeared, and 12 hours later, bleeding, necrosis, and inflammatory cell infiltration occurred. The advantage of this model is that it is simple and avoids non-specific system effects caused by drugs. It is similar to human bile reflux pancreatitis, but sometimes it only produces mild pancreatitis. Runzi et al. improved this method. After the proximal end of the duodenum was cut 10cm, the two ends were closed and ligated the common bile duct. The stomach and duodenum were anastomosed, so that pancreatic juice flowed into the closed loop, and as its internal pressure increased, reflux occurred. Acute necrotizing pancreatitis developed, edema pancreatitis occurred 4 hours after operation, and hemorrhage and necrosis occurred 9-12 hours after operation. In addition, there is also the use of pancreatic duct ligation and pancreatic artery or vein blockade to produce acute pancreatitis.

　　5. Feeding method

　　choline ethionine reared female rats to make an acute pancreatitis model, while male rats are not sensitive to drug stimulation. The young mice were fed with choline-free ethionine, and pancreatic necrosis and abdominal fat necrosis occurred 4 days later. The principle may be that the secretion of pancreatic acinar caused by choline-free ethionine is blocked, and zymogen granules and lysosomes are activated in the cell.

　　6. Secretion promoting method

　　``Using bombesin analog CCK-PZ intravenously or subcutaneously to increase the secretion of pancreatic proteolytic enzymes to a level that can cause pancreatic acinar autolysis.

　　7. Isolated pancreatitis model

　　The isolated extracorporeal perfusion technique is mainly used to free the pancreas and duodenum, and intubate the splenic artery, mesenteric artery, portal vein and pancreatic duct; then remove the pancreas and connect it to an oxygen and perfusion circulator that can control temperature and humidity; after stable perfusion for 30 minutes , Infusing free fatty acids from the artery to simulate alcoholic pancreatitis; blocking the pancreatic duct and intravenous injection of bombesin to produce biliary pancreatitis; making ischemic pancreatitis for 2 h.