利拉鲁肽对非酒精性脂肪肝大鼠脂联素及胰岛素抵抗的影响

Effects of liraglutide on adiponectin and insulin resistance in rats with non-alcoholic fatty liver disease

目的:观察利拉鲁肽(Lira)对非酒精性脂肪肝(NAFLD)大鼠血清和肝组织脂联素(ADP)及胰岛素抵抗的影响。方法:雄性SD大鼠30只,随机分为3组,分别予普通饮食(ND组)10只、高脂饮食(HFD组)10只和高脂饮食加利拉鲁肽腹腔注射(Lira组)10只。高脂饮食12周建立大鼠NAFLD模型,建模成功后Lira组予利拉鲁肽腹腔注射治疗4周。16周末处死各组大鼠,生物化学法检测丙氨酸氨基转移酶(ALT)、空腹血糖(FBG)、甘油三酯(TG)及总胆固醇(TC),分光光度计测定游离脂肪酸(FFAs),酶联免疫吸附法测定胰岛素和ADP。结果:与HFD组比较,Lira组大鼠体质量、肝指数、胰岛素抵抗指数、血清TG、TC、ALT、FBG及肝匀浆TG、TC、FFAs显著下降(均P<0.05),血清及肝组织ADP明显升高(P<0.05),肝脏脂肪变性程度明显减少至恢复正常(P<0.05),肝组织ADP含量与肝脏FFAs含量呈负相关。结论:利拉鲁肽改善胰岛素抵抗和肝脏脂肪变的可能机制之一与其升高血清及肝组织脂联素水平有关。

AIM： To investigate the effects of glucagon-like peptide 1 analog, liraglutide, on adiponectin and insulin resistance in the rats with diet-induced non-alcoholic fatty liver disease （NAFLD）. METHODS ：. Male rats were randomly divided into 3 groups ： normal diet （ND） group （ n = 10）, high-fat diet （HFD） group （ n = 10）, and HFD with intraperitoneal injection of liraglutide group （n = 10, first 12 weeks with HFD, later 4 weeks with liraglutide）. All treat ments continued for 16 weeks, and then the rats were killed ethically and the blood samples and liver tissues were collect ed. The levels of alanine aminotransferase （ALT）, fasting blood glucose （FBG）, total cholesterol （TC） and triglyceride （TG） were detected by a biochemical automatic analyzer. The levels of free fatty acids （FFAs）, fasting insulin （FINS） and adiponectin were measured by RIA and ELISA. RESULTS： Compared with HFD group, the body weight, liver index, homeostasis assessment-insulin resistance （ HOMA-IR）, the serum levels of TG, TC, ALT and FBG, and the liver levels of TG, TC and FFAs in the rats in liraglutide group were apparently lower, the degree of hepatic steatosis and inflammatory activity significantly decreased （P 〈 O. 05 ）, and the level of adiponectin in the serum and liver homogenate increased ob viously （ P 〈 0.05 ）. The level of adiponectin in the liver homogenate was negatively correlated with the levels of FFAs in the liver homogenate. CONCLUSION： Liraglutide is beneficial for NAFLD rats to improve insulin resistance and reduce hepatic steatosis by increasing the level of adiponectin in the serum and liver tissues.