LXRα靶基因对肾阳虚实验大鼠血脂中胆固醇的调控机制研究

Research of regulation mechanisms on hyperlipidemia cholesterol by the LXRα target gene in kidney- yang deficiency syndrome rats

目的通过肾阳虚高脂血症模型,观察右归丸对模型大鼠LXRα靶基因ABCA1和CETP表达的影响,以探讨LXRα靶基因在肾阳虚引起高脂血症中的表达及其意义。方法利用大剂量肌注氢化可的松制作肾阳虚高脂血症大鼠模型,给予右归丸进行干预,检测实验大鼠肝脏的肝指数及肝组织病理变化,通过蛋白免疫印迹检测外周血中ABCA1和CETP蛋白表达,通过RTPCR检测各组实验大鼠外周血ABCA1和CETPmRNA的表达。结果肌注氢化可的松模型组大鼠肝脏肉眼观察颜色变黄、肥腻,肝脏出现明显的脂肪变性;右归丸组大鼠肝脏脂肪变明显较模型组大鼠轻,肝湿重也小于模型组(P<0.05);与正常组比较,右归丸组和模型组肾阳虚高脂血症大鼠外周血ABCA1和CETP蛋白和基因表达增加(P<0.05),与模型组比较,右归丸组大鼠外周血ABCA1和CETP基因表达减少(P<0.05)。结论模型组大鼠具有高脂血症性脂肪肝的特征,其机制可能是通过上调LXRα靶基因ABCA1和CETP表达;右归丸可能通过抑制LXRα靶基因的表达来降低模型大鼠胆固醇的含量。

Objective By kidney- yang deficiency hyperlipidemia model to observe the effect of Youguiwan LXRαtarget gene ABCA1 and CETP expression in rat model interference with Youguiwan,to investigate LXRα target gene deficiency caused by hyperlipidemia expression and its significance. Methods The production of high- dose intramuscular hydrocortisone rat model of hyperlipidemia,observation intervention effects on the liver in rats by hepatic pathological changes in liver index intervened with Youguiwan,by protein Western blot detection of ABCA1 and CETP protein expression in peripheral blood,and detected ABCA1 and CETPmRNA expression by RT-PCR in each group peripheral blood. Results Intramuscular hydrocortisone rat liver showed color yellow,fatty liver,cells showed a significant steatosis; the Youguiwan group hepatic steatosis in rats significantly lighter than the model rats,liver wet weight is less than the model group( P< 0. 05); compared with the normal group,Youguiwan and model groups ABCA1 and CETP protein and gene expression increased in peripheral blood of rats( P< 0. 05); compared with the model group,the Youguiwan group ABCA1 and CETP gene of model rats in the peripheral blood are reduced( P< 0. 05). Conclusion The model rats with hyperlipidemia has fatty liver characteristics,which may be regulated by LXRα target genes ABCA1 and CETP expression; Youguiwan may inhibit the expression of LXRα target gene models to reduce cholesterol levels in rats.