丹酚酸A对异丙肾上腺素致小鼠心肌缺血的保护作用及其机制

摘要

Aim To investigate the effect of Salvianol-ic acid A (Sal A)on mice with isoproterenol (ISO)-induced myocardial infraction and its possible mecha-nisms.Methods The mice were subcutaneously in-jected with ISO (8 mg·kg-1 )to induce myocardial in-farction.The myocardial protective effect of Salvianolic acid A was evaluated from mortality rate,electrocardio-gram (ECG),heart function,myocardial infarction in-dex,serum myocardial enzymes and its action mecha-nisms were explored from inflammation,anti-oxidation and cells apoptosis.Results Salvianolic acid A dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardi-al protection effects.ELISA results showed that Salvi- anolic acid A could reduce the expression of myocardial inflammatory cytokines such as IL-6(interleukin-6,IL-6),TNF-α(tumornecrosis factor-α,TNF-α).West-ern-blotting confirmed that Salvianolic acid A could in-crease the expression of anti-apoptotic proteins Bcl-2, reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.Con-clusion Salvianolic acid A displays a significant pro-tective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to the in-crease of PI3K/Akt signal pathway and the inhibition of cell apoptosis and inflammatory reaction.%目的：丹酚酸 A 是我国传统中药丹参中提取的主要水溶性成分之一，本研究探讨了丹酚酸 A 抗异丙肾上腺素诱导的小鼠心肌缺血的作用及其机制。方法采用皮下注射异丙肾上腺素（isopropranol，ISO）8 mg·kg －1致小鼠心肌缺血模型，从动物死亡率、心电图、心脏指数、血清心肌酶谱以及病理切片评价丹酚酸 A 对小鼠心肌的保护作用，并从抗氧化、炎症以及细胞凋亡通路探讨其作用机制。结果丹酚酸 A 能够剂量依赖性地增强心肌缺血小鼠的心脏功能，减少心肌损伤酶的漏出，改善缺血心肌的病理变化，具有明显的心肌保护作用。丹酚酸 A 能降低心肌炎症因子白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumornecrosis factor-α，TNF-α）的水平，减少 ISO 损伤引起的心肌细胞凋亡，增加抗凋亡蛋白 Bcl-2表达，降低促凋亡蛋白 Bax 表达，