安徽医科大学学报Issue(6)：721-725,5.
非诺贝特保护非酒精性脂肪性肝病小鼠胰岛素抵抗作用机制的探讨
Protective effects of fenofibrate on insulin resistance in mice of nonalcoholic fatty liver disease and its partly mechanisms of action
摘要
Abstract
Objective To study whether the protective effects of fenofibrate on insulin resistance in mice of nonal-coholic fatty liver disease(NAFLD) are related to endoplasmic reticulum stress (ERS). Methods Male C57BL/6 mice were fed with high-calorie and high-cholesterol diet ( HCD) to induce a model of NAFLD, then one of those two groups from HCD was treated with fenofibrate 40 mg/( kg · d ) for 2 weeks ( HCF ) . Glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to analyze the improvement on insulin resistance. The serum levels of triglyceride ( TG) , total cholesterol ( TC) , high density lipoprotein-cholesterol ( HDL-C) , low density lip-oprotein-cholesterol ( LDL-C) , alanine aminotransferase ( ALT) and aspartic transaminase ( AST) were detected. The pathological changes of livers were detected with HE and Oil Red O staining, the mRNA and protein expression of peroxisome proliferator-activated receptorα( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP) were detected with real-time quantification PCR and Western blot analysis respectively. Results Compared with the SCD mice, the HCD mice showed significant insulin resistance, higher serum levels of TG, TC and LDL-C (P<0. 01, P<0. 05), lower serum level of HDL-C (P<0. 01), micro-and macrovesicular steatosis, ballooned hepatocytes and infiltration of inflammatory cells were observed in the liver, the expressions of PPARα and GRP78 at mRNA and protein levels were decreased (P<0. 05), however, the expressions of CHOP at mRNA and protein levels were increased ( P<0 . 05 ) . Fenofibrate intervention significantly improved insulin resist-ance and decreased the serum level of TG ( P<0. 05 ) . Fenofibrate also alleviated hepatic steatosis and inflammato-ry infiltration, and increased the mRNA and protein expressions of PPARα and GRP78, decreased the mRNA and protein expression of CHOP ( P<0 . 05 ) . Conclusion Fenofibrate significantly improves insulin resistance and de-creases the serum level of TG in NAFLD mice, which may be related to activating PPARα and relieving ERS.关键词
非诺贝特/非酒精性脂肪性肝病/胰岛素抵抗/内质网应激/PPARαKey words
fenofibrate/nonalcoholic fatty liver disease/insulin resistance/endoplasmic reticulum stress/PPARα分类
医药卫生引用本文复制引用
沈馨茹,鲁云霞,章秋..非诺贝特保护非酒精性脂肪性肝病小鼠胰岛素抵抗作用机制的探讨[J].安徽医科大学学报,2014,(6):721-725,5.基金项目
安徽省自然科学基金(编号:1208085MH168、1308085MH154) （编号:1208085MH168、1308085MH154）
安徽医科大学博士启动基金(编号:XJ201013) （编号:XJ201013）
