姜黄素后处理通过血红素氧合酶1发挥对心肌缺血/再灌注损伤的保护作用

Protective Effects of Curcumin Post-treatment on Myocardial Ischemia /Reperfusion Injury via Heme Oxygenase-1

目的探讨姜黄素后处理对心肌缺血/再灌注(I/R)损伤的作用及其可能的机制。方法选用48只雄性SD大鼠随机分为4组:假手术组、I/R组、姜黄素后处理组和姜黄素+ZnPPⅨ后处理组。结扎雄性SD大鼠冠状动脉左前降支,使心肌缺血30 min,再灌注6 h造成心肌缺血再灌注损伤模型,并于缺血30 min后再灌注前1分钟内由舌下静脉推注姜黄素或ZnPPⅨ。检测各组大鼠的心肌病理改变以及心功能改变、血浆中乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量以及心肌组织中血红素氧合酶1(HO-1)活性和表达改变。结果与I/R组比较,姜黄素后处理可明显上调HO-1活性和表达,并能显著抑制I/R后的心肌氧化应激损伤反应。这一保护作用可被HO-1抑制剂ZnPPⅨ部分消除。结论姜黄素后处理可通过抗氧化作用减轻心肌I/R损伤,其保护作用与上调HO-1蛋白的活性和表达有关。

Aim To investigate the effects of curcumin post-treatment on oxidative stress injury induced by myocardial ischemia /reperfusion（I /R） and its mechanism. Methods Forty-eight male SD rats were randomized into four groups： sham group,I /R group,curcumin post-treatment group and curcumin ＋ Zinc protoporphrinⅨ（ZnPPⅨ） post-treatment group. Myocardial I /R was carried out by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 6 h,and injection of curcumin or ZnPPⅨ before reperfusion via sublingual vein. Blood was collected at the end of reperfusion for detecting changes of myocardial pathologic changes,cardiac function,serum lactate dehydrogenase（LDH）,superoxide dismutase（SOD） and malondialdehyde（MDA）. Heme oxygenase-1（HO-1） activity and expression in myocardial tissue was detected by HO-1 activity detection kit and Western blot. Results Compared with I /R group,post-treatment with curcumin resulted in an enhanced activity and expression of HO-1 protein,and reduced oxidative stress injury induced by I /R（P 〈 0. 05）. This protective effect was considerably attenuated by ZnPPⅨ（an inhibitor of HO-1）.Conclusions Curcumin post-treatment could protect against myocardial I /R injury via anti-oxidative injury and up-regulation activity and expression of HO-1 protein,which was a main component in curcumin-mediated protective effect.