纳洛酮对大鼠缺血再灌注心肌细胞凋亡及Fas、FasL表达的影响

Effect of naloxone on apoptosis and expression of Fas and FasL protein in rats with myocardial ischemia-reperfusion injury

目的:观察纳洛酮(naloxone,Nal)对大鼠缺血再灌注心肌细胞凋亡及Fas、FasL蛋白表达的影响并探讨其机制。方法:SD大鼠24只,随机分成假手术组(Sham组)、缺血再灌注组(IR组)和纳洛酮处理组(Nal组)。原位末端标记法(TUNEL)检测心肌细胞凋亡情况;蛋白免疫印迹法(Western blotting)检测Fas、FasL蛋白表达;光镜下观察心肌组织病理学的改变。结果:与Sham组相比,IR组可见大量心肌细胞凋亡,Fas、FasL蛋白表达显著增加(P<0.01)。与IR组相比,Nal组心肌细胞凋亡显著减少,Fas、FasL蛋白表达明显降低(P<0.01)。IR组见心肌组织呈大小不等的灶性坏死,Nal组心肌坏死不明显。结论:心肌缺血再灌注时Fas、FasL表达介导心肌细胞凋亡,纳洛酮通过抑制Fas、FasL蛋白的表达而减少细胞凋亡从而起到保护心肌的作用。

Objective：To observe the effect of naloxone（Nal） on cardiomyocyte apoptosis and expression of Fas and FasL following acute ischemia-reperfusion injury in vivo and to explore its mechanism.Methods：Twenty-four SD rats were selected and randomly divided into three groups：sham-operated group（sham group）,ischemia-reperfusion group（IR group）,IR and treated with naloxone group（Nal group）.Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling（TUNEL） and Western blotting were used respectively to detect the cardiomyocyte apoptosis and protein expressin of Fas and FasL,and histopathological changes of myocardium were observed by optic microscopy.Results：Numerous apoptotic cardiomyocytes were found and the expression of Fas and FasL were increased significantly in ischemic fields in the IR group as compared to sham group（P 〈 0.01）,apoptosis and the expression of Fas and FasL were decreased significantly in the Nal group as compared with IR group（P 〈 0.01）.Local myocytes lesions were observed in myocardium in the IR group,but the injury was lessened significantly in the Nal group.Conclusion：The expression of Fas and FasL in ischemia-reperfusion myocardium can induce cardiomyocyte apoptosis,and naloxone has the cardioprotective effects in ischemia-reperfusion injury by significantly inhibiting the cardiomyocyte apoptosis induced by Fas and FasL expression.