牛舌草总黄酮抗大鼠心肌缺血再灌注损伤的作用及机制

Effect and mechanism of total flavonoids of bugloss on rats with myocardial ischemia and reperfusion injury

牛舌草是维吾尔医长期实践中治疗心脑血管疾病的常用药材之一。本研究采用大鼠冠状动脉左前降支结扎30 min,复灌4 h模拟临床心肌缺血再灌注(ischemia/reperfusion,I/R)损伤,于再灌注后腹腔注射给予10、30和50 mg·kg-1牛舌草总黄酮(bugloss total flavonoids,BTF),根据心电图、心功能、心肌梗死指数和血清心肌酶谱结果评价牛舌草总黄酮的心肌保护作用,并从炎症、细胞凋亡以及PI3K/Akt信号通路等探讨其作用机制。实验结果显示,牛舌草总黄酮能够剂量依赖性地降低心肌梗死指数,改善缺血再灌注大鼠的心脏功能,减少心肌酶的漏出,具有明显的心肌保护作用。ELISA结果表明,牛舌草总黄酮能降低心肌炎症因子IL-1β、IL-6、TNF-α的水平,增加Bcl-2,降低Bax,并上调PI3K和Akt的磷酸化水平。牛舌草总黄酮具有明显的抗心肌缺血再灌注损伤作用,其机制可能与上调PI3K/AKT信号通路而抑制细胞凋亡与炎症有关。

Abstract： This study is to investigate the effect of total flavonoids of Uygur medicine bugloss （BTF） on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending （LAD） coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg -kg-~. Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTE Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. EL1SA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1 β, IL-6 and TNF-α. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through uore^ulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.