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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 study the effects of berberine (BBR) on attenuating myocardial ischemia-reperfusion (MI / R) injury in rats and its regulation of Notch1 / Hes1 signal. Methods 100 male SD rats were randomly divided into five groups: Sham, MI / R + solvent group, MI / R + BBR treatment group, Sham + solvent Group (Sham + V), Sham + BBR group. MI / R model was induced in the left anterior descending coronary artery of the ligation group, myocardial ischemia 30 min, 4 h after reperfusion, the intracellular region (NICD) and the ratio of Hes1, PTEN, p-Akt / Akt Apoptosis-related protein expression was detected. Cardiomyocyte apoptosis, infarct size and oxidative stress were detected 6 hours after reperfusion, and cardiac function was measured 72 hours after reperfusion. Results Ischemia-reperfusion injury significantly reduced left ventricular ejection fraction and shortening of left ventricular shortening, increased myocardial apoptosis, infarct size, serum lactate dehydrogenase and creatine kinase levels, while BBR treatment significantly improved cardiac function Reduce myocardial apoptosis and infarction. In addition, BBR treatment could significantly activate cardiac Notch1 / Hes1 signaling pathway and regulate PTEN / Akt signaling, thereby decreasing myocardial apoptosis (all P <0.01). Conclusion BBR treatment can significantly reduce myocardial infarction and apoptosis after MI / R injury and improve cardiac function. At the same time, BBR treatment can significantly upregulate Notch1 / Hes1 signal after myocardial ischemia and play a regulatory role on PTEN / Akt signaling and downregulate cardiac apoptotic signal.