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目的:探讨白蛋白激酶C-β抑制剂LY333531对早期糖尿病大鼠心脏抗氧化状态及NADPH氧化酶的影响。方法:24只SD雄性大鼠(240-260 g),随机分为正常对照组(NC)、糖尿病组(DM)及糖尿病LY333531治疗组(LY)。4周后试剂盒检测血浆及心肌组织中的15-F2t-Isoprostane与总抗氧化浓度,HE染色光镜观察心肌形态学变化。Western bolt分析NADPH氧化酶亚基P22phox、P67phox及gP91phox蛋白水平改变。结果:与NC组比较,DM组心肌组织结构紊乱,血浆与心肌组织中15-F2t-Isoprostane及总抗氧化浓度水平明显增加,P22phox与gP91phox蛋白表达水平明显上调,P67phox膜转位明显增强(P<0.05)。与DM组比较,LY组心肌组织结构趋于正常,血浆与心肌组织中15-F2t-Isoprostane及血浆总抗氧化浓度水平明显减少,P22phox蛋白表达水平明显下调,P67phox膜转位明显减弱(P<0.05),但不能改变gP91phox表达水平。结论:LY333531通过抑制NADPH氧化酶表达的增加及活性的增强,减少糖尿病大鼠心肌组织的氧化损伤,从而发挥其心脏保护作用。
Objective: To investigate the effect of LY333531, an inhibitor of albumin kinase C-β, on the cardioresenchymal antioxidant status and NADPH oxidase in early diabetic rats. Methods: Twenty-four male Sprague-Dawley rats (240-260 g) were randomly divided into normal control group (NC), diabetic group (DM) and diabetic LY333531 treatment group (LY). After 4 weeks, the 15-F2t-Isoprostane and total anti-oxidant concentrations in plasma and myocardium were detected by using the kit. The morphological changes of myocardium were observed by HE staining. Western bolt analysis of NADPH oxidase subunits P22phox, P67phox and gP91phox protein levels change. Results: Compared with NC group, the myocardial structure was disorganized in DM group. The levels of 15-F2t-Isoprostane and total antioxidant capacity in plasma and myocardium were significantly increased, the expressions of P22phox and gP91phox were significantly up-regulated and P67phox was significantly up-regulated <0.05). Compared with DM group, the myocardial tissue structure in LY group tended to be normal, the levels of 15-F2t-Isoprostane and plasma total anti-oxidant concentration in plasma and myocardial tissue were significantly decreased, P22phox protein expression was significantly decreased, P67phox membrane translocation was significantly decreased (P < 0.05), but could not change the expression level of gP91phox. CONCLUSION: LY333531 can exert its cardioprotective effect by inhibiting the increase of NADPH oxidase expression and activity, reducing the oxidative damage of myocardial tissue in diabetic rats.