周脂素和 ADRP在糖代谢异常大鼠肝脏组织中的表达

摘要

[ ABSTRACT] AIM:To observe the changes of perilipin and adipose differentiation-related protein ( ADRP) du-ring the development of diabetes mellitus and to explore the effect of perilipin and ADRP on abnormal glucose metabolism with non-alcoholic fatty liver disease ( NAFLD) .METHODS:The rat model of impaired glucose tolerance ( IGT) was in-duced by feeding high-fat diet, and the type 2 diabetes mellitus (T2DM) model was induced by feeding high-fat diet for 4 weeks and intraperitoneally injecting streptozotocin.The morphological change of the liver tissue was observed under optical microscope.The serum contents of perilipin and ADRP were measured by ELISA.The mRNA expression of perilipin and ADRP in the liver tissues was detected by real-time PCR.The protein expression of ADRP in the liver tissues was deter-mined by Western blotting.RESULTS:HE staining showed steatosis in the liver of the rats in IGT group was more serious than that in T2DM group.The biochemical and the pathological processes of rat models were consistent with the clinical feature of related diseases.The serum content of perilipin had no difference among various groups.The mRNA expression of perilipin in IGT group and T2DM group was significantly higher than that in control group.Compared with IGT group, the mRNA expression of perilipin in T2DM group was significantly increased.The serum content of ADRP in T2DM group was significantly lower than that in control group.The mRNA and protein expression of ADRP in model groups was signifi-cantly lower than that in control group.Compared with IGT group, the mRNA expression of ADRP in T2DM group was sig-nificantly reduced.CONCLUSION: The serum content of ADRP plays a role in the development and progression of T2DM.It is negatively correlated with HOMA-IR.NAFLD occurs during progression of abnormal glucose metabolism in-duced by feeding high-fat diet.The development of abnormal glucose metabolism with NAFLD is probably related to the in-creased expression of perilipin and the reduced expression of ADRP.%目的：探讨脂滴相关蛋白周脂素（perilipin）和脂肪分化相关蛋白（ADRP）在糖尿病发生发展过程中的变化情况以及在糖代谢异常合并非酒精性脂肪肝中的作用。方法：分别用高脂饲料喂养和高脂饲料喂养加小剂量链脲佐菌素建立糖耐量受损（IGT）和2型糖尿病大鼠模型（T2DM），采用光镜观察各组大鼠肝组织的形态学改变；用ELISA法测定血清周脂素perilipin和ADRP含量；real-time PCR技术检测肝脏组织中perilipin和ADRP mRNA的表达；用Western blotting法检测肝脏组织中ADRP蛋白的表达。结果：HE结果显示， IGT组和 T2DM组大鼠均有肝细胞脂肪变性，IGT组变性更严重；各模型组的生化指标与临床相关疾病的表现一致；血清perilipin水平各组之间无差异，但IGT组和T2DM组肝组织perilipin mRNA表达明显升高（P＜0.01）；与IGT组相比，T2DM组perilipin mRNA表达显著增加（P＜0.05）。 T2DM组血清ADRP含量较其对照组明显降低（P＜0.01）；模型组肝组织ADRP mRNA表达明显降低（ P＜0.01）；ADRP蛋白表达较其对照组也明显降低（ P＜0.01）；与IGT组相比， T2DM组ADRP mRNA表达明显降低（ P＜0.01）。结论：血清ADRP含量在T2DM的形成中起一定的作用，与胰岛素抵抗指数呈明显负相关；高脂喂养后能导致大鼠糖代谢异常，并伴有非酒精性脂肪肝的发生；糖代谢异常合并非酒精性脂肪肝的发生可能与肝组织perilipin表达升高和ADRP表达降低有关。