苯那普利后处理对大鼠缺血再灌注心肌细胞凋亡及NF-κB表达的影响

Protective Effects of Benazepril Postconditioning on Apoptosis and NF-κ B Expression of Cardiomyocy-tes with Ischemic Reperfusion

目的观察苯那普利后处理对大鼠心肌缺血再灌注（I/R）心肌细胞凋亡和核因子-κB（NF-κB）表达的影响,初步探讨其可能的作用机制。方法应用Langendroff离体灌流装置,采用完全停灌复灌的方法制作离体大鼠心肌缺血再灌注模型。将32只SD大鼠随机等分为4组,对照组、I/R组、缺血预处理组、苯那普利后处理组。改良亮绿变色酸法（GCA）观察心肌损害程度;免疫组化法检测心肌组织中核因子-κB（NF-κB）的表达;原位末端标记法（TUNEL）测定组织中细胞凋亡率。结果与对照组比,I/R组心肌损害程度增加（P〈0.01）,免疫组织化学染色可见NF-κB蛋白表达显著增强（P〈0.01）,细胞凋亡率明显升高（P〈0.01）。与I/R组相比,苯那普利后处理组GCA染色心肌变性减轻,阳性率减低（14±7）%vs（40±17）%,（P〈0.01）,NF-κB表达减少（34.8±4.7）%vs（49.3±9.7）%,P〈0.05）,细胞凋亡率明显下降（13±1.7）%vs（18.5±2.5）%,（P〈0.01）。苯那普利后处理组和预处理组相比较,差异无统计学意义（P〉0.05）。结论苯那普利后处理具有明显降低大鼠缺血再灌注后心肌细胞凋亡的作用,其机制可能与苯那普利后处理抑制NF-κB参与的细胞凋亡有关。

Objective To evaluate the effects of benazepril postconditioning on cardiac myocyte apoptosis and the expression of nuclear NF-κB during ischemia-reperfusion（I/R） in isolated rats hearts,and investigate the possible mechanism.Methods Thirty-two male Sprague-Dawley rats were isolated and perfused using the Langendorff mode with modified Kreb-Henseleit （KH） buffer and were randomly assigned into four groups：control group,I/R group,Preconditioning group,benazepril postconditioning group.Apoptosis cell was estimated by TUNEL staining,myocardial infarction size was examined by Gonori chromotropic acid staining（GCA）.The NF-κ B was investigated by immunohistochemical technique.Results Compared with control,I/R caused a marked increase in the infarction size （P0.01）and the expression of NF-κB （P0.01）,increased apoptosis percentage（P0.01）.Compared with I/R group,benazepril postconditioning decreased apoptosis percentage（13±1.7）%vs（18.5±2.5）%,（P0.01）,decreased the infarction size （14±7）%vs （40±17）%,（P0.01）and the expression of NF-κB （34.8±4.7）%vs（49.3±9.7）%,（P0.05）.There was no difference between benazepril postconditioning group and preconditioning group （P0.05）.Conclusion Benazepril postconditioning can relieve cardiac myocyte apoptosis following myocardial ischemic/reperfusion injury,which may be related to a decrease in over expression of NF-κB in the ischemia/reperfusion myocardium.