罗格列酮对2型糖尿病并发非酒精性脂肪肝大鼠肝脏解偶联蛋白-2表达的影响

Effect of rosiglitazone on the expression of hepatic uncoupling protein 2 in type 2 diabetic rats complicated with non-alcoholic fatty liver disease

目的观察罗格列酮对2型糖尿病(T2DM)并发非酒精性脂肪肝(NAFLD)大鼠肝脏解偶联蛋白-2(UCP-2)表达的影响,探讨其防治T2DM并发NAFLD的部分作用机制。方法高脂高糖饮食结合小剂量链脲佐菌素(STZ)腹腔注射建立T2DM并发NAFLD大鼠模型,将成模大鼠随机分为模型组、罗格列酮治疗组,每组各16只,并设立正常对照组。治疗组给予罗格列酮3 mg/(kg.d)灌胃治疗。于实验第16(治疗后8周)、20周(治疗后12周)末分批处死大鼠,检测肝功能、空腹血糖、血脂和血清胰岛素水平,光镜下观察大鼠肝脏组织学形态,分别以免疫组织化学法和逆转录-聚合酶链反应(RT-PCR)法检测肝组织UCP-2蛋白和UCP-2mRNA的表达情况。结果与正常组相比,模型组大鼠血清转氨酶、空腹血糖、血清胰岛素及血脂水平均明显升高,胰岛素敏感指数明显下降(P均<0.01),肝脏出现不同程度脂肪变性,肝组织UCP-2蛋白和UCP-2 mRNA表达增高,以20周末最为明显。在16周末(治疗后8周)和20周末(治疗后12周),治疗组大鼠血清转氨酶、血糖、血清胰岛素及血脂水平均有改善,胰岛素敏感指数明显升高,肝细胞脂肪变性明显减轻,肝组织UCP-2蛋白和UCP-2 mRNA表达明显下降,与模型组比较差异均有统计学意义(P<0.01)。结论 T2DM并发NAFLD大鼠肝组织UCP-2表达增强,罗格列酮可以调控T2DM并发NAFLD大鼠肝脏UCP-2 mRNA和UCP-2蛋白的适度表达,这可能是其治疗T2DM并发NAFLD的分子机制之一。

Objective To observe the effect of rosiglitazone on the expressions of uncoupling protein-2（UCP-2） in the liver of type 2 diabetic rats complicated with non-alcoholic fatty liver disease（NAFLD）,and explore its mechanism of treating type 2 diabetes mellitus（T2DM） complicated with NAFLD.Methods The model rats of T2DM complicated with NAFLD were established by feeding high-glucose and high-fat diet,and injection of low dose streptozotocin.The model rats were randomly divided into 2 groups： model group（n=16） and rosiglitazone group（n=16）.Twenty normal rats were set for normal control group.Intragastric administration lasted for 12 weeks.At the end of 16 weeks（after treated 8 weeks） and 20 weeks（after treated 12 weeks）,the levels of serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,fasting blood glucose（FBG）,fasting insulin（FINs）,triglyceride（TG）,total cholesterol（TC） and free fatty acid（FFA） in each group were tested and the level of insulin sensitivity index（ISI） was calculated.Meanwhile,pathological changes of liver,the expression of UCP-2 mRNA and UCP-2 protein of liver tissues in each group were detected.Results The levels of serum ALT,AST,FBG,FINs,serum TG,TC and FFA were significantly higher（all P0.01）,ISI was signifcantly lower（P0.01）,liver cirrhosis was significantly exacerbated,and the expressions of UCP-2 mRNA and UCP-2 protein were signifcantly increased（all P0.01） in model group compared with control group.After treatment for 8 weeks and 12 weeks with rosiglitazone,the levels of serum ALT,AST,FBG,serum TG,TC and FFA were signifcantly decreaseed,ISI was signifcantly increased（P0.01 or P0.05）,liver cirrhosis was significantly improved,and the expressions of UCP-2 mRNA and UCP-2 protein were signifcantly decreased（P0.01） compared with model rats.Conclusion Rosiglitazone can control the appropriate expression of liver tissue UCP-2 mRNA and UCP-2 protein of type 2 diabetic rats complicated with NAFLD.It is likely to be one of the important mechanisms in treating T2DM complicated with NAFLD.