中文摘要：

目的观察urantide对大鼠缺血/再灌注心肌组织氧化应激损伤的作用和心肌细胞凋亡的影响及其与PI3K/Akt及PKC信号通路的关系。方法可逆性冠脉左前降支结扎造成心肌缺血/再灌注模型,给予大鼠心脏缺血30 min再灌注90 min。80只大鼠随机分为假手术组、缺血/再灌注（I/R）组、urantide低、中、高剂量组（3,10,30μg.kg-1）、维拉帕米对照组（1.6 mg.kg-1）、urantide＋CHE组（30μg.kg-1＋1 mg.kg-1）、urantide＋LY294002组（30μg.kg-1＋0.3 mg.kg-1）。Urantide低、中、高剂量组中urantide于缺血前5 min舌下静脉1 min内一次性推注,urantide＋CHE组与urantide＋LY294002组中,在穿线稳定后舌下静脉分别快速推注CHE与LY294002,5 min后舌下静脉快速推注uran-tide 30μg.kg-1,稳定10 min后再行缺血/再灌注操作。实验结束后测定大鼠血清中超氧化物歧化酶（SOD）、一氧化氮合酶（NOS）活力和丙二醛（MDA）含量以及一氧化氮（NO）含量。TUNEL法检测凋亡细胞指数（AI）,免疫组化法检测心肌组织Bcl-2、Bax的蛋白表达。结果与I/R组相比,urantide 30μg.kg-1能明显升高SOD活性（P〈0.01）,明显减少血清中MDA的含量（P〈0.05）,明显提高NOS活力（P〈0.01）,使NO含量增加（P〈0.01）;Bax蛋白表达和心肌细胞凋亡指数降低（P〈0.01）,Bcl-2蛋白表达增加（P〈0.05）;urantide＋CHE组与urantide＋LY294002组与urantide30μg.kg-1组相比,SOD活力和NO含量下降,MDA含量上升,心肌组织中Bax蛋白表达和心肌细胞凋亡指数上升,而Bcl-2蛋白表达下降,与I/R组比较差异无统计学意义（P〉0.01）。结论 Urantide能够通过激活PKC和PI3K/Akt信号转导通路,减少心肌组织氧自由基的含量,进一步调控Bcl-2和Bax蛋白的表达,抑制心肌缺血/再灌注大鼠心肌细胞的凋亡,从而对大鼠心肌缺血/再灌注具有一定保护作用。

英文摘要：

Aim To investigate the regulation of pretreatment with urantide in cardiomyocyte apoptosis by PI3K/Akt and PKC signaling pathway in ischemiareperfusion myoeardial injury of rats. Methods Male SD rats were randomized into eight groups： sham group, model （ ischemia/reperfusion injury） group, urantide low,middle, high dose groups （3,10,30μg.kg-1 ） , verapamil group （ 1.6 mg.kg-1 ）, urantide ＋ CHE group（30μg.kg-1＋1 mg.kg-1） , urantide ＋ LY294002 group （30μg.kg-1＋0.3 mg.kg-1）. Myocardial IR was carried out by ligation of left anterior descending coronary artery for 30 rain followed by reperfusion for 90 rain. Different drugs were administered by intravenous injection before the ligation in rats. The ehanges of ST wave at different time were determined by electroeardiogram（ECG）. The activities of superoxide dismutase （SOD） and NOS and content of malondialdehyde（MDA） and NO in the serum of rats in different groups were measured. The apoptotic index of myoeyte was measured by TUNEL method. The Bcl- 2 protein and Bax protein expression was also measured by immunohistochemistry. Results It was found that the administration of urantide could significantly decrease the the level of MDA, increase activities of SOD and NOS, then increase nitric oxide （NO） production. Moreover, treatment with urantide markedly reduced myocyte apoptotic death. Urantide also ameliorated the increased Bax protein expression and decreased Bcl-2 protein expression and ratios of Bcl-2 to Bax. However, all these effects were completely abolished by PKC inhibitor CHE and PI3K/Akt inhibitor LY294002. Conclusion Urantide exerted beneficially cardioprotective effect on rats with myocardial ischemia/reperfusion injury, mainly scavenging oxidative stress-triggered over- generation and accumulation of ROS, alleviating myocardial ischemia injury induced apoptosis by activating PKC and PI3K/Akt signaling pathways.