链脲佐菌素诱导糖尿病大鼠NO变化对缺血再灌注损伤的影响

目的:探讨链脲佐菌素(STZ)诱导的不同周期糖尿病对心肌缺血/再灌注(I/R)损伤的影响及其与血浆一氧化氮(NO)变化的关系.方法:阻断和开放左冠状动脉前降支建立大鼠急性心肌I/R模型.分别用TTC染色测定大鼠心肌I/R后梗死面积;用硝酸还原酶法测定NO含量;用免疫印迹法定量分析代表细胞生存信号的磷酸化蛋白激酶B(P-Akt)的表达.结果:STZ处理后2周,糖尿病组(2WD+I/R)心肌梗死面积比相应周期对照组(2WC+I/R)明显缩小,STZ处理后16周(16WD+I/R),梗死面积比相应对照组(16WC+I/R)增加;血浆NO水平在2周糖尿病组中较对照组增高,但是在16周糖尿病组中较对照组显著减少;P-Akt在心肌的表达在2WD组比2WC组增加35%,在16WD组比16WD组明显减少.结论:STZ诱导的急、慢性期糖尿病对心肌I/R损伤呈现相反的作用.这可能是由于急、慢性期糖尿病相反的NO改变而引起的.

Effects of STZ-induced diabetes on ischemia/reperfusion injury of rat myocardium via alterations in NO levels

Objective To determine the effects of different-term STZ-induc ed diabetes on ischemia/reperfusion(I/R)injury of myocardium and if I/R injury i s related to diabetes-induced alterations in NO levels.Methods A rat model of I/R injury was established by the occlusion and reperfusion of left descending c oronary artery(LDCA).Size of I/R-induced infarct was determined using triphen yltetrazolium chloride(TTC)staining;NO production was quantified by nitrite/n itrate colormetric method;Phosphorylation of protein kinase B(P-Akt)expressi on featuring cell survival signaling was quantified by Western blot analysis.Re sult Two weeks after STZ treatment,infarct size was decreased in the 2 weeks of diabetic hearts(2WD)as compared with time-matched control group(2WC),whereas after 16 weeks of diabetes(16WD),the infarct size was increased in the diabeti c hearts as compared with the 16WC group.Plasma NO levels were increased in 2WD rats whereas NO levels were markedly decreased in 16WD group compared with time-matched controls.P-Akt expression was increased in 2WD group by 35%over 2WC values whereas there was a decrease in P-Akt expression in both 16WD and 16WC group.Conclusion Short-and long-term STZ-induced diabetes exert opposite eff ects on myocardial I/R injury,and these contradictory effects may depend on diff erent alterations in NO levels.