Xuan Feifei, Jian Jie
Department of Pharmacology, Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
Int J Mol Med. 2016 Jul;38(1):328-36. doi: 10.3892/ijmm.2016.2615. Epub 2016 May 31.
Epigallocatechin gallate (EGCG), a polyphenol derived from green tea, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. In this study, the cardioprotective effects of EGCG on myocardial ischemia/reperfusion (I/R) injury in rats and the underlying mechanisms were investigated. A rat model of I/R injury was established by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. The levels of I/R-induced creatine kinase-MB (CK-MB) and the release of lactate dehydrogenase (LDH), as well as the infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined and compared. Western blot analysis was carried out to elucidate the potential molecular mechanisms of action of EGCG. The results revealed that EGCG post-conditioning significantly decreased the levels of CK-MB and the release of LDH, reduced the myocardial infarct size, decreased the apoptotic rate and partially preserved heart function. Furthermore, EGCG decreased the expression of cleaved caspase-3 concomitantly with the upregulation of PI3K, and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). It also inhibited I/R-induced overautophagy and promoted the clearance of autophagosomes, as evidenced by a decrease in the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, the downregulation of Beclin1, Atg5 and p62, and the upregulation of active cathepsin D. Additionally, we observed an increase in the phosphorylation levels of the mammalian target of rapamycin (mTOR) following treatment with EGCG. Taken together, the findings of this study demonstrate that, EGCG post-conditioning alleviates myocardial I/R injury by inhibiting apoptosis and restoring the autophagic flux, which is associated with several targets of the PI3K/Akt signaling pathway.
表没食子儿茶素没食子酸酯（EGCG）是一种从绿茶中提取的多酚，具有广泛的生物活性，包括抗氧化、抗动脉粥样硬化和抗肿瘤活性。在本研究中，研究了EGCG对大鼠心肌缺血/再灌注（I/R）损伤的心脏保护作用及其潜在机制。通过结扎左冠状动脉前降支30分钟，然后再灌注2小时，建立I/R损伤大鼠模型。检测并比较I/R诱导的肌酸激酶同工酶MB（CK-MB）水平、乳酸脱氢酶（LDH）释放、梗死面积、心肌细胞凋亡和心脏功能损害。进行蛋白质免疫印迹分析以阐明EGCG潜在的分子作用机制。结果显示，EGCG后处理显著降低了CK-MB水平和LDH释放，减小了心肌梗死面积，降低了凋亡率，并部分保留了心脏功能。此外，EGCG降低了裂解的半胱天冬酶-3的表达，同时上调了PI3K、Akt和内皮型一氧化氮合酶（eNOS）的磷酸化水平。它还抑制I/R诱导的过度自噬并促进自噬体的清除，微管相关蛋白1轻链3（LC3）-II/LC3-I比值降低、Beclin1、Atg5和p62下调以及活性组织蛋白酶D上调证明了这一点。此外，我们观察到用EGCG处理后哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化水平增加。综上所述，本研究结果表明，EGCG后处理通过抑制细胞凋亡和恢复自噬流减轻心肌I/R损伤，这与PI3K/Akt信号通路的几个靶点有关。
