醛糖还原酶抑制剂对糖尿病大鼠肾小球蛋白激酶C活性的影响

The Effection of Aldose Reductase Inhibitors on the Activity of Glomerulus Protein Kinase C (PKC) of Diabetic Rat

目的探讨醛糖还原酶抑制剂Sorbinil对糖尿病大鼠肾小球蛋白激酶C活性的影响。方法 采用腹腔内注射链脲菌素法制作糖尿病大鼠模型,将大鼠分为模型组、Sorbinil组、格列喹酮+苯那普利组和正常对照组。8周后处死大鼠,分离肾小球,分别测定各组肾小球细胞浆和细胞膜蛋白激酶C活性。结果糠尿病模型组细胞浆蛋白激酶C活性显著降低,细胞膜蛋白激酶C活性显著升高。用两组西药治疗后,苯那普利+格列奎酮组无明显改善,而Sorbinil组可显著提高细胞浆蛋白激酶C活性、降低细胞膜蛋白激酶C活性。结论Sorbinil可通过改善多元醇代谢而降低蛋白激酶C活性,同时,亦或存在其他途径如直接对蛋白激酶C的抑制作用等等。Sorbinil通过调节多元醇代谢等途径间接或直接降低蛋白激酶C活性,是其治疗糖尿病肾病的作用机理之一。

Objective To study the effection of aldose reductase inhibitors on the activity of glomer-ulus protein kinase C (PKC) of diabetic rat. Methods The rats were divided four groups: diabetes inel-litus group, sorbinil group, gliquidone and benazepril group and the control. The rats were killed after eight weeks. The glomerulus were separated and their PKC activity of cell plasm and cell membrane were determinated. Results The PKC activity of cell plasm was decreased and the PKC activity of cell membrane was increased in the diabetic rat obviously. Sorbinil cculd increase the PKC activity of cell plasm and decrease the PKC activity of cell membrane, while there was no changes in the gliquidone and benazepril group. Conclution Sorbinil could derease the PKC activity by ameliorating the metabolism of poly-ethanol or there existed other ways to inhibit the PKC. activity. One of the mechanism of sorbinil curing diabetes mellitus was that it could derease the PKC activity by ameliorating the metabolism of ployetha-nol.