厄贝沙坦联合卡维地洛对心肌梗死后心衰大鼠心肌氧化应激的作用及可能机制

Effect and mechanism of irbesartan combined with carvedilol on myocardial oxidative stress in rats with heart failure after myocardial infarction

目的 探究厄贝沙坦联合卡维地洛对心肌梗死后心衰大鼠心肌氧化应激的作用及可能机制。方法30只SD大鼠随机分为假手术组(Sham组)、模型组(Model组)和厄贝沙坦联合卡维地洛组(Irbesartan+carvedilol组),每组10只。超声诊断仪检测大鼠心功能,HE染色观察大鼠心肌病理学改变,TUNEL检测大鼠心肌细胞凋亡,ELISA检测大鼠心肌组织氧化应激因子水平,荧光探针检测大鼠心肌组织活性氧水平,Western blot检测心肌组织Notch1、JAK2和STAT3蛋白表达水平。结果 厄贝沙坦联合卡维地洛降低大鼠心脏左心室舒张末径,增加射血分数和短轴缩短率,改善心肌组织病理损伤,降低心肌组织细胞凋亡水平,降低心肌组织MDA含量和ROS水平,增加SOD活性,增加心肌组织Notch1、JAK2和STAT3蛋白表达水平。结论 厄贝沙坦联合卡维地洛改善心肌梗死所致心衰大鼠心肌损伤,降低心肌细胞凋亡和氧化应激,其机制可能与激活Notch1/JAK2/STAT3信号通路有关。

Objective To explore the effect and possible mechanism of irbesartan combined with carvedilol on myocardial oxidative stress in rats with heart failure after myocardial infarction. Methods Thirty SD rats were randomly divided into sham group, model group and irbesartan+carvedilol group, with 10 rats in each group. Cardiac function of rats was detected by ultrasonic diagnostic instrument, pathological changes of myocardium were observed by HE staining,apoptosis of myocardium cells was detected by TUNEL, oxidative stress factor level of myocardium tissue was detected by ELISA, reactive oxygen species level of myocardium tissue was detected by fluorescence probe. Western blot was used to detect Notch1, JAK2 and STAT3 protein expression in myocardial tissue. Results Irbesartan combined with carvedilol reduced left ventricular end-diastolic diameter, increased ejection fraction and short-axis shortened rate, improved pathological injury of myocardial tissue, decreased apoptosis level of myocardial tissue, decreased MDA content and ROS level of myocardial tissue, increased SOD activity, and increased protein expression of Notch1, JAK2 and STAT3 in myocardial tissue. Conclusion Irbesartan combined with carvedilol can improve myocardial injury and reduce apoptosis and oxidative stress in myocardial failure rats induced by myocardial infarction, which may be related to the activation of Notch1/JAK2/STAT3 signaling pathway.