腹腔注射四氯化碳辅以饮食改良制备犬慢性肝纤维化模型

Induction of Liver Fibrosis and Cirrhosis in a New Canine Model by Using Intraperitoneal Injection of CCl_4 Plus Diet Modification

探讨一种经典的、与人类慢性肝纤维化——肝硬化进程相似的大动物模型建立方法.采用15只成年健康中华田园犬:对照组5只,使用生理盐水腹腔注射及正常饲料干预;实验组10只,采用小剂量四氯化碳(CCl4)腹腔注射及高脂饮食干预.间断采血检测肝功能、血清学肝纤维化指标,B超引导下定期肝穿活检作HE染色和Masson染色.56周后所有实验动物成功诱导至不同程度的肝纤维化.丙氨酸氨基转移酶、门冬氨酸转氨酶、球蛋白、总胆红素、γ-谷氨酰基转肽酶以及透明质酸与对照组相比,差异均有统计学意义(P<0.05).联合应用小剂量CCl4和单纯高脂饮食可成功诱导犬慢性肝纤维化-肝硬化模型,该方法动物存活率和成模率均较高,可为后续的相关研究提供更好的平台.

To explore the procedures for creating a classic large animal model that mimics the chronic disease progress of hepatic fibrosis and cirrhosis in human subjects. Fifteen adult cross-bred dogs were divided into two groups： the normal control group （n=5） received intraperitoneal injection of normal saline and normal diet, and the experimental group （n=10） were administered 50% CCl4 in vegetable oil by intraperitoncal injection and high fat diet. Every 4 weeks after injection, blood samples in all animals were collected and analyzed to monitor the liver function and serum markers of liver fibrosis. Additionally, ultrasound-guided liver biopsy was performed for HE and Masson staining. Different degree of liver cirrhosis in subjects from the experimental group was successfully induced at the end of 56 week. The serum level of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, globulin （GLB）, total bilirubin （TBIL）, γ-glutamyl transferase （GGT） and hyaluronic acid （HA） in the experimental group were significantly increased relative to the control group （P〈0.05）. A chronic hepatic fibrosis and cirrhosis animal model could be established in Chinese rural dog by a method of combining CCl4 injection in low dosage and pure high-fat diet administration. This method showed a high rate of model duplication and yielded low subject mortality, which would provide a favorable foundation for the related studies in the future.