摘要
目的研究小檗碱(BBR)减轻大鼠心肌缺血再灌注(MI/R)损伤的作用及其对心肌Notch1/Hes1信号的调控。方法 100只雄性SD大鼠随机分为五组:假手术组(Sham)、MI/R+溶剂组(MI/R+V)、MI/R+BBR治疗组(MI/R+BBR)、Sham+溶剂组(Sham+V)、Sham+BBR组。行结扎大鼠冠状动脉左前降支手术造成MI/R模型,心肌缺血30 min,再灌注4 h后检测心肌Notch1受体胞内区(NICD)及Hes1、PTEN、p-Akt/Akt比值和凋亡相关蛋白表达,再灌注6 h后检测心肌细胞凋亡率、梗死面积及氧化应激相关指标,再灌注72 h后检测心功能。结果缺血再灌注损伤显著下调左心射血分数与左心室短轴缩短率,增加心肌凋亡率、梗死面积、血清乳酸脱氢酶及肌酸肌酶水平,而BBR治疗可显著改善心功能并减轻心肌凋亡及梗死。另外,BBR治疗可显著激活心肌Notch1/Hes1信号通路并调控PTEN/Akt信号,从而下调心肌凋亡信号(均P<0.01)。结论 BBR治疗可显著减轻MI/R损伤后心肌梗死及凋亡水平,改善心功能。同时,BBR治疗可显著上调缺血打击后心肌Notch1/Hes1信号并对PTEN/Akt信号发挥调控作用,下调心肌凋亡信号。
Objective To explore the ameliorative effect of berberine（BBR） on myocardial ischemia/ reperfusion（MI/ R） in-jury in rats and its influence on myocardial Notch1/ Hes1 signaling pathway.Methods 100 male Sprague-Dawley rats were randomlyassigned to 5 groups： Sham, MI/ R＋V（vehicle）, MI/ R＋BBR, Sham＋V and Sham＋BBR, and then exposed to myocardial ischemia/reperfusion（MI/ R） surgery. After 4 h of reperfusion, myocardial NICD（Notch1 intracellular domain）, Hes1, PTEN, p-Akt/ Akt ra-tio and apoptotic related protein espressions were measured. After 6 h of reperfusion, myocardial apoptotic index and infarct size were e-valuated. The cardiac function were measured 72 h after reperfusion.Results BBR treatment significantly improved the cardiac func-tional recovery and reduced myocardial apoptosis. Additionally, BBR treatment also modulated PTEN/ Akt signaling by activatingNotch1/ Hes1 signaling.Conclusion This study showed that BBR protected the heart against MI/ R injury by reducing apoptosis possi-bly through Notch1/ Hes1 signaling pathway.
出处
《中国体外循环杂志》
2015年第4期240-244,共5页
Chinese Journal of Extracorporeal Circulation
基金
国家自然科学基金(81470415
81270170
81200151
81470411)
国家十二五科技支撑计划课题(2011BAI11B20)
陕西省国际科技合作与交流计划项目(2015KW-047)
陕西省社会发展攻关计划(2015SF104
2012K15-02-01)
西京医院学科助推计划(XJZT14203
XJGX12C11
XJGX13LC15)
