自发性2型糖尿病大鼠主动脉胰岛素受体底物1与eNOS的蛋白表达

Insulin receptor substrate 1 and eNOS expression in aortas from OLETF rats

应用免疫组织化学和Western印迹方法 ,测定 16周及 2 4周自发性 2型糖尿病OLETF大鼠主动脉胰岛素受体底物 1(IRS 1)和内皮型一氧化氮合酶 (eNOS)的蛋白表达 ,以同种系非糖尿病LETO大鼠作为正常对照 ,以探讨胰岛素受体后信号传递分子IRS 1与胰岛素抵抗状态下大血管病变的关系。结果显示IRS 1和eNOS在主动脉内膜呈阳性表达 ;OLETF大鼠呈胰岛素抵抗特征 ,在 16周和 2 4周其主动脉组织内IRS - 1的蛋白表达水平均明显低于对照组 ,分别减少 2 8 2 %和 33 9% (P <0 0 1)。eNOS蛋白水平分别减少 2 7 7%和 35 8% (P <0 0 1)。两者变化方向一致。提示血管组织胰岛素受体后信号传递分子异常 ,导致内皮细胞胰岛素抵抗及一氧化氮生成障碍 ,可能是糖尿病患者早期大血管病变危险性增加的机制之一。

To explore potential linkage between IRS 1 and macroangiopathy in insulin resistant states, the expression of IRS 1 and eNOS in aortas from OLETF rats was examined by immunohistochemistry and Western blot analysis. Both IRS 1 and eNOS positive immunostaining were found in the intima. Compared with non diabetic controls at 16th week and 24th week, the protein level of IRS 1 decreased by 28.2% and 33.9%( P <0.01), eNOS protein decreased by 27.7% and 35.8%( P <0.01) respectively in aorta of OLETF rats. The change of IRS 1 protein was consistent with that of eNOS protein. These results suggested that the reduction of IRS 1 protein expression may result in insulin resistance of endothelial cells and may be responsible for the development of diabetic macroangiopathy.