六味地黄丸改善OLETF鼠肝脏胰岛素抵抗的实验研究  

Protective effects of Liuweidihuangwan on hepatic insulin resistance in OLETF rats

作　　者：杜华[1] 薛耀明[1] 朱波[1] 

机构地区：[1]南方医科大学南方医院内分泌代谢科,广东广州510515

出　　处：《南方医科大学学报》2012年第12期1824-1827,共4页Journal of Southern Medical University

基　　金：广东省中医药局科研课题(2009454)

摘　　要：目的探讨六味地黄丸改善2型糖尿病大鼠模型中肝细胞胰岛素抵抗的作用机制。方法以正常LETO鼠为LETO组,OLETF鼠分为不加药的对照组以及予六味地黄丸加药的干预组,分别于8、32、40周龄随机处死,收集肝组织。制作病理切片观察各组肝脏组织形态学改变,RT-PCR检测PEPCK表达改变以及免疫印迹(Western blot)检测IRS-1、IRS-2蛋白表达。结果与LETO组相比,对照组肝脏细胞随着时间延长出现明显的小叶结构破坏以及肝脏脂肪变性,而干预组小叶结构基本正常,仅有轻度脂肪变性。RT-PCR检测显示对照组PEPCK表达显著高于LETO组(P<0.01),而给予六味地黄丸的干预组PEPCK的表达则显著低于对照组(P<0.01)。免疫印迹检测对照组p-IRS-1和p-IRS-2蛋白表达水平显著低于LETO组以及干预组(P<0.05)。结论六位地黄丸通过抑制肝脏中糖异生关键酶PEPCK的活性以及提高胰岛素信号通路中IRS-1和IRS-2的表达,改善肝细胞的胰岛素抵抗。Objective To investigate the mechanism through which Liuweidihuangwan improves hepatic insulin resistance in type 2 diabetic rats. Methods With LETO rats as the normal control group, OLETF rats were treated daily with or without Liuweidihuangwan. At 8, 32, and 40 weeks of the treatment, 3 rats were randomly selected from each group for histological examination of the liver tissues and for detection of phosphoenolpyruvate carboxylase kinase （PEPCK） mRNA expression using RT-PCR and insulin receptor substrate-1 （IRS-1） and IRS-2 protein expressions using Western blotting. Results Compared with LETO rats, OLETF rats showed progressive destruction of the lobular structures and hepatic steatosis in the liver over time. OLETF rats with Liuweidihuangwan treatment had basically normal lobular structure with only mild fatty degeneration in the liver. RT-PCR detection demonstrated a significantly higher PEPCK mRNA expression in untreated OLETF rats than in LETO rats （P〈0.01）, but a significantly lowered PEPCK expression in OLETF rats after Liuweidihuangwan dosing （P〈 0.01）. Western blotting showed that significantly lower p-IRS-1 and p-IRS-2 protein expressions in untreated OLETF rats than those in LETO rats and treated OLTEF rats （P〈0.05）. Conclusion Liuweidihuangwan improves hepatic insulin resistance in OLETF rats by inhibiting the activity of gluconeogenic key enzyme （PEPCK） in the liver and enhancing IRS-1 and IRS-2 expressions in the insulin signaling pathway.

关 键 词：六味地黄丸 胰岛素抵抗 磷酸烯醇式丙酮酸羧激酶 胰岛素受体底物 

分 类 号：R285.5[医药卫生—中药学]