肝X受体在肥胖或高血糖状态下的表达及其对肝PEPCK表达的影响

Expression of LXR in rats with obesity or hyperglycemia and its impact on PEPCK expression in liver

目的:观察在大鼠肥胖或高血糖状态下肝内肝X受体(LXR)表达的变化情况及其对下游靶基因11β-羟基类固醇脱氢酶1(11β-HSD1)mRNA和磷酸烯醇式丙酮酸羧激酶(PEPCK)mRNA表达的调节作用,探讨LXR信号通路对糖代谢的影响机制。方法:SD雄鼠27只分为正常对照(CON)组、糖尿病(DM)组和肥胖(OB)组,后2组诱导成模后测定各组大鼠的体质量、血糖、胆固醇和三酰甘油。对CON组和OB组大鼠行腹部MRI检查、正葡萄糖高胰岛素钳夹试验和肝脏病理切片检查,采用实时荧光定量PCR检测各组大鼠肝脏LXR mRNA、PEPCK mRNA和11β-HSD1 mRNA的表达情况。结果:MRI及肝病理切片显示OB组大鼠腹腔脂肪严重堆积及脂肪肝形成,OB组大鼠较CON组具有明显的胰岛素抵抗。与CON组相比,各实验组大鼠肝LXR mRNA表达均显著升高,11β-HSD1 mRNA表达均显著下降,OB组肝PEPCK mRNA表达明显下调,DM组肝PEPCK mRNA表达较明显上调(P均<0.05)。结论:在肥胖状态下,LXR可能作为糖代谢的保护性受体,通过调节肝糖代谢酶,使血糖保持稳态;进入糖尿病阶段后,LXR的保护作用并不能逆转因胰岛素不足所致的糖代谢相关酶的异常改变,因而血糖升高。

Objective To investigate the expression of LXR in rats with obesity or hyperglycemia and its impact on the regulation of expressions of 11β-HSD1 mRNA and PEPCK mRNA to study the mechanism of impact of LXR signal pathway on glucose metabolism.Methods Twenty-seven male SD rats were modeled and categorized into three groups： normal control（CON） group,obesity（OB） group and diabetes mellitus（DM） group.Weight,blood glucose,serum triglyceride and cholesterol were measured to estimate the metabolic status.Abdominal MRI and liver biopsy were performed to estimate fat accumulation,and glucose clamp test was performed to estimate the insulin resistance status.Then the rats were sacrificed and liver was taken for pathological examination.Real-time PCR was used to determine the liver expression of LXR mRNA,PEPCK mRNA and 11β-HSD1 mRNA.Results MRI and the liver pathological study showed that the OB group had severe abdominal fat accumulation and fatty liver.And the glucose clamp test showed that the rats in OB group had obvious insulin resistance.Comparing to CON group,the LXR mRNA expression was significantly higher and the 11β-HSD1 mRNA expression was significantly lower in OB and DM groups;PEPCK mRNA expression decreased significantly in OB group,while it was significantly higher in DM group（P0.05）.Conclusions In obesity status,LXR as a protective receptor of glucose metabolism may keep glucose homeostasis through regulating hepatic glucose metabolic enzymes.Whereas in diabetes period,the protective effect of LXR could not reverse the abnormal alteration of glucose metabolism related enzymes caused by insufficiency of insulin,thereby blood glucose is elevated.