大麻素受体1在大鼠非酒精性脂肪性肝病的实验研究

Role of the endocannabinoid receptor 1 in the rat of non-alcoholic fatty liver disease

目的观察大麻素受体1(CB1R)在大鼠非酒精性脂肪性肝病(NAFLD)模型中的表达情况,并使用CB1R拮抗剂利莫那般评价对NAFLD的治疗作用,探究其可能机制。方法采用高糖高脂饲料(HSHF)建立大鼠NAFLD模型,分组并连续给药8周,取动物血清和肝脏,通过免疫组织化学染色方法检测肝组织CB1R在实验组的表达情况,通过苏木素-伊红染色(HE)、酶联免疫吸附实验(ELISA)、血清生化检测,观察利莫那般对肝脏组织病理学、肝功能酶学、血脂等的影响。结果 CB1R在模型组的表达与对照组、干预组比较显著增加(P<0.01),利莫那般可逆转肝组织脂肪变性,降低血清leptin、TNF-α、丙氨酸氨基转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)的含量,与模型组比较,差异有统计学意义(P<0.01)。结论采用HSHF饲料喂养大鼠30 d成功建立NAFLD模型,CB1R拮抗剂有望成为NAFLD治疗的潜在靶点。

Objective To observe the expression of receptor 1 （CB1R） in the rat model of nonalcoholic fatty liver disease （NAFLD） and evaluate the therapeutic role of CB1R antagonist Rimonabant in NAFLD, then study that the possible mechanisms. Methods After fed with HSHF diet for 30 days, the rats randomly allocated in several groups, then injected daily with Rimonabant for 8 weeks. Serum enzymes of liver function and serum lipid were detected.Liver steatosis were evaluated by histopathology. The expressions of CB1R in the liver tissue were evaluated by immunohis-tochemical technique. Results The expression of CB1R in model groups was higher than that of groups （P 〈 0.01）. After an intervention with Rimonabant, the liver steatosis gradually reversed and serum leptin, serum TNF-α, serum alanine aminotransferase （ALT）, serum aspartate aminotransferase （AST）, triglyceride （TG）, total cholesterol （TC） were significantly decreased （P 〈 0.01）. Conclusion The model of the NAFLD is successfully induced by HSHF diet for 30 days. CB1 receptor antagonist will be a promising target for the pharmacologic treatment approach of NAFLD.