白藜芦醇对胰岛素抵抗模型中同型半胱氨酸代谢关键酶的调控

目的 探讨在胰岛素抵抗动物模型中白藜芦醇（RES）对同型半胱氨酸(Hcy)代谢关键酶调控的分子机制。方法 6周健康SD大鼠利用高脂高糖饮食加高脂灌胃3个月制造胰岛素抵抗模型。确定胰岛素抵抗模型建立成功后，随机分为胰岛素抵抗组和白藜芦醇干预组，每组10只。胰岛素抵抗组继续高脂高糖饮食，白藜芦醇干预组高脂高糖饮食加30mg/(kg·d)白藜芦醇灌胃。8周后，空腹状态下测定每组体重和血浆中Hcy、葡萄糖(GLU)、胰岛素(INS)、甘油三酯(TG)和总胆固醇(TC)的浓度，计算胰岛素抵抗指数（IRI）；免疫组织化学、RT-PCR和Western blotting检测肝脏组织亚甲基四氢叶酸还原酶（MTHFR）、胱硫醚合成酶（CBS）、蛋氨酸合成酶（MTR)表达的变化。 结果 白藜芦醇干预组和胰岛素抵抗组比较，空腹GLU、INS、TG的浓度降低（P<0.05）, IRI降低（P<0.05），Hcy浓度降低（P<0.05），体重和TC差异无统计学意义（P>0.05）。MTHFR和CBS的mRNA及蛋白表达水平升高（P<0.05），MTR的mRNA及蛋白表达差异无统计学意义（P>0.05）。 结论 胰岛素抵抗条件下，白藜芦醇可能通过上调MTHFR和CBS的表达，促进同型半胱氨酸的转化，可能在减轻胰岛素抵抗中具有关键的作用。

Regulation of resveratrol to key enzyme in homocysteine metabolism in insulin resistance model

Objective To investigate the regulation mechanism of resveratrol(RES) on key enzymes of homocysteine metabolism for SD rats with insulin resistance.
Methods Six weeks healthy mice were made as the insulin resistance model with diet by high fat and sugar and gavage by high fat for 3 months. The rats were randomly divided into the insulin resistance group (n=10)and the resveratrol intervention group (n=10). High fat and sugar were fed in the insulin resistance group for eight weeks. The resveratrol intervention group was fed by high fat and sugar and gavage by resveratrol［30mg/（kg·d)］ for eight weeks. The concentrations of homocysteine, glucose, insulin, total cholesterol and triglyceride were measured in the fasting state. The insulin resistance index (IRI) was calculated. The expressions of methylenetetrahydrofolate reductase (MTHFR), cystathionine β synthase (CBS) and methionine synthetase (MTR) were detected by immunohistochemical, RT-PCR and Western blotting in the rat liver tissue. Results The concentrations of the blood glucose, blood insulin and triglyceride in the resveratrol intervention group were lower than that in the insulin resistance group (P<0.05). The ISI was lower in the resveratrol intervention group. The concentration of homocysteine was decreased (P<0.05). However, the weight and the concentration of total cholesterol were no statistical significance (P>0.05). The protein expressions of MTHFR and CBS in the resveratrol intervention group were higher compared with the insulin resistance group by Western blotting and immunohistochemical staining(P<0.05).The mRNA expressions of MTHER and CBS in the resveratrol intervention group were higher compared with the insulin resistance group by RT-PCR. However, the expression of MTR protein and mRNA were not different between the resveratrol intervention group and the insulin resistance group (P>0.05). Conclusion Resveratrol can improve the expression of the MTHFR and CBS which participate the metabolism of homocysteine and facilitate the transformation of homocysteine, thus it may play a key role in alleviating insulin resistance.