摘要目的 评价盐酸戊乙奎醚预先给药对大鼠心肌缺血再灌注时核因子E2相关因子2(Nrf2)/抗氧化反应序列原件(ARE)信号通路的影响.方法 清洁级健康雄性SD大鼠36只,体重220～240 g,2～3月龄,采用随机数字表法分为3组(n=12):假手术组(S组)、心肌缺血再灌注组(Ⅰ/R组)和盐酸戊乙奎醚预先给药组(PHC组).采用结扎左冠状动脉前降支30 min恢复灌注的方法制备大鼠心肌缺血再灌注损伤模型.于缺血前30 min时PHC组腹腔注射盐酸戊乙奎醚2 mg/kg,S组仅穿线,不结扎.于再灌注120 min时处死大鼠取心脏,采用TTC法确定心肌梗死体积,计算心肌梗死体积百分比,TUNEL法检测凋亡心肌细胞,计算细胞凋亡指数,Western blot法和实时荧光定量PCR法分别检测Nrf2、血红素氧合酶-1(HO-1)、醌氧化还原酶1(NQO1)、γ-谷氨酸半胱氨酸合成酶(γ-GCS)及其mRNA表达.结果 与S组比较,Ⅰ/R组和PHC组心肌梗死体积百分比和细胞凋亡指数增加,Nrf2、HO-1、NQO1、γ-GCS及其mRNA表达下调(P＜0.05);与Ⅰ/R组比较,PHC组心肌梗死体积百分比和细胞凋亡指数降低,Nrf2、HO-1、NQO1、γγ-GCS及其mRNA表达上调(P＜0.05).结论 盐酸戊乙奎醚预先给药通过激活Nrf2/ARE信号通路减轻大鼠心肌缺血再灌注损伤.

abstractsObjective To evaluate the effect of penehychdine hydrochloride pretreatment on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway during myocardial ischemia-reperfusion (Ⅰ/R) in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 2-3 months,weighing 220-240 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),myocardial Ⅰ/R group and penehyelidine hydrochloride pretreatment group (group PHC).Myocardial Ⅰ/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.At 30 min before ischemia,penehyelidine hydrochloride 2 mg/kg was injected intraperitoneally in group PHC,and the anterior descending branch of left coronary artery was only exposed but not ligated in group S.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL) and expression of Nrf2,heme oxygenase-1 (HO-1),NQO1 and γ-glutamylcysteine synthetase (γ-GCS) protein and mRNA (by using Western blot or real-time fluorescence quantitative polymerase chain reaction).The percentage of myocardial infarct size and apoptosis index were calculated.Results Compared with group S,the percentage of myocardial infarct size and apoptosis index were significantly increased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was down-regulated in Ⅰ/R and PHC groups (P＜0.05).Compared with group l/R,the percentage of myocardial infarct size and apoptosis index were significantly decreased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was up-regulated in group PHC (P＜0.05).Conclusion Penehyclidine hydrochloride pretreatment attenuates myocardial Ⅰ/R injury through activating Nrf2-ARE signaling pathway in rats.