摘要
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 explore the effects of PKC-β inhibitor LY333531 on myocardial NADPH oxidase in early diabetic rats.Methods： Twenty-four male SD rats were randomly assigned to control group（NC）,diabetic group（DM） and diabetic group with LY333531（LY） treatment for four weeks.The levels of 15-F2t-Isoprostane and total antioxidant concentration in plasma and heart tissues were assessed by Reagent kit.Morphological changes of cardiomyocytes were observed under light microscope with hematoxylin-eosin staining.The subunits P22phox,P67phox and gP91phox of NADPH oxidase were analyzed by Western blot.Results： The structure of cardiac tissues in DM group was disordered,LY treatment made it close to normal.The 15-F2t-Isoprostane levels and total antioxidant concentrations in plasma and heart tissues,the protein expression of P22phoxand gP91phox,and the membrane translocation of P67phox were significantly increased in diabetic group as compared to control group（all P0.05）.LY treatment decreased the levels of 15-F2t-Isoprostane in plasma and heart tissues,as well as plasma total antioxidant concentration,P22phox expression,and membrane translocation of P67phox as compared to control group（P0.05）,but there was not a significant change in gP91phox expression.Conclusion： The LY333531 may protect diabetic myocardium from oxidative injury through inhibiting NADPH oxidase activation and expression.
出处
《武汉大学学报（医学版）》
CAS
北大核心
2011年第2期141-145,F0002,共6页
Medical Journal of Wuhan University
基金
国家自然科学基金资助项目(编号:30872447)
