Department of Pharmacy, Yantaishan Hospital, Yantai, China.
Eur Rev Med Pharmacol Sci. 2021 Sep;25(17):5490-5499. doi: 10.26355/eurrev_202109_26658.
To investigate the pharmacodynamic mechanism of curcumin against myocardial ischaemia-reperfusion injury by regulating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/rapamycin target protein (mTOR) signalling pathway.
The left anterior descending coronary artery was ligated for 30 min and reperfused for 3 h to establish an ischaemia-reperfusion injury model. The electrocardiogram (ECG) detection of rats was performed, and the degree of myocardial infarction was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of serum creatine kinase isoenzyme (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO) and other related indicators were detected. The protein expressions of mTOR, phosphorylated (p)-mTOR, AKT and p-AKT were detected by Western blotting, whereas the expressions of Bcl-2 and Bax were detected by real-time polymerase chain reaction.
The results showed that compared with the model group, curcumin could improve the ECG findings, reduce the scope of myocardial infarction, reduce the expression levels of CK-MB, LDH, AST, MDA, NO and increase those of SOD and GSH. Curcumin can also down-regulate the expression of Bax and up-regulate the protein levels of Bcl2, p-mTOR and p-AKT (p < 0.05 or p < 0.01).
This study shows that curcumin has a significant protective effect on myocardial ischaemia-reperfusion, and its mechanism may be related to the activation of PI3K/AKT/mTOR signalling pathway and inhibition of inflammation, apoptosis and oxidative stress.
通过调节磷脂酰肌醇-3 激酶(PI3K)/蛋白激酶 B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路,研究姜黄素对心肌缺血再灌注损伤的药效机制。
结扎大鼠左前降支 30 min 后再灌注 3 h 建立缺血再灌注损伤模型。对大鼠进行心电图(ECG)检测,并通过 2,3,5-三苯基氯化四氮唑染色确定心肌梗死程度。检测血清肌酸激酶同工酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、一氧化氮(NO)等相关指标的表达水平。采用 Western blot 检测 mTOR、磷酸化(p)-mTOR、AKT 和 p-AKT 的蛋白表达水平,实时聚合酶链反应检测 Bcl-2 和 Bax 的表达。
与模型组相比,姜黄素能改善心电图表现,缩小心肌梗死范围,降低 CK-MB、LDH、AST、MDA、NO 的表达水平,增加 SOD 和 GSH 的表达水平。姜黄素还能下调 Bax 的表达,上调 Bcl2、p-mTOR 和 p-AKT 的蛋白水平(p<0.05 或 p<0.01)。
本研究表明姜黄素对心肌缺血再灌注具有显著的保护作用,其机制可能与激活 PI3K/AKT/mTOR 信号通路和抑制炎症、细胞凋亡及氧化应激有关。