中国药理学通报2013，Vol.29Issue(5)：648-654,7.DOI:10.3969/j.issn.1001-1978.2013.05.013
Urantide对大鼠心肌缺血/再灌注后心肌细胞凋亡的作用及机制研究
Regulation of urantide in PI3K/Akt and PKC signaling transduction in myocardial ischemia-reperfusion injury to relieve the cardiomyocyte apoptosis in rats and its mechanism
摘要
Abstract
Aim To investigate the regulation of pre- treatment with urantide in cardiomyocyte apoptosis by PI3K/Akt and PKC signaling pathway in ischemia-reperfusion myocardial 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 (3,10,30 μg · kg-1 ), verapamil group( 1. 6 mg · kg-1 ), urantide + CHE group( 30 μg · kg-1 + 1 mg · kg-1 ), urantide + LY294002 group( 30 μg · kg-1 +0. 3 mg · kg-1 ). Myocardial IR was carried out by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 90 min. Different drugs were administered by intravenous injection before the ligation in rats. The changes of ST wave at different time were determined by electrocardiogram( 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 myocyte 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.关键词
urantide/心肌缺血/再灌注损伤/氧化应激/细胞凋亡/PKC信号通路/PI3K/Akt信号通路Key words
urantide/ ischemia-reperfusion injury/ ROS/ apoptosis/ PKC signaling pathway/ PI3K/Akt signaling pathway分类
医药卫生引用本文复制引用
张骏艳,姚华,李晟,孙璇君,陈志武..Urantide对大鼠心肌缺血/再灌注后心肌细胞凋亡的作用及机制研究[J].中国药理学通报,2013,29(5):648-654,7.基金项目
国家自然科学基金资助项目(No 81173596) （No 81173596）
安徽省自然科学基金资助项目(No 11040606M196) （No 11040606M196）
