1 Department of Cardiology, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, People's Republic of China.
2 Department of Cardiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
J Cardiovasc Pharmacol Ther. 2019 Nov;24(6):551-558. doi: 10.1177/1074248419845916. Epub 2019 May 2.
Coronary microembolization (CME)-induced cardiomyocyte apoptosis is the primary factor in causing cardiac dysfunction. Resveratrol (RES) is known to play a protective role in a variety of cardiovascular diseases, yet it is not known whether RES has a protective role in CME. Therefore, the effect of RES on cardiomyocyte apoptosis and cardiac function damage which are induced by CME in rats was investigated in this study.
Fifty Sprague-Dawley rats were separated into 5 groups randomly (10 rats were included in each): sham group, CME group, RES+CME group, RES+CME+Sirtuin-1 (SIRT-1) inhibitor EX527 (RES+CME+EX) group, and CME+EX group. Cardiac function, serum c-troponin I (cTnI) level, apoptotic index, and microinfarct were measured by cardiac ultrasound, myocardial enzyme assessment, TdT-mediated dUTP Nick-end labeling and hematoxylin-basic fuchsin-picric acid staining. The levels of p53, p53 acetylation, SIRT-1, Bax, Bcl-2, and cleaved caspase-3 were detected by Western blot.
Myocardial dysfunction, enhanced apoptotic index as well as cTnI were caused after the operation of CME. Coronary microembolization induced increased expression of p53 acetylation and cleaved caspase-3, while the SIRT-1 and Bcl-2/Bax ratio was reduced. The CME effect was reversed by RES while EX527 attenuated this protective effect.
Resveratrol can improve cardiac function, in the sense that it attenuates CME-induced cardiomyocyte apoptosis, which is perhaps associated with its inhibition pro-apoptotic pathway of p53 which is transcription-independent.
冠状动脉微栓塞（CME）诱导的心肌细胞凋亡是导致心功能障碍的主要因素。白藜芦醇（RES）已知在多种心血管疾病中发挥保护作用，但尚不清楚 RES 是否对 CME 具有保护作用。因此，本研究旨在探讨 RES 对 CME 诱导大鼠心肌细胞凋亡和心脏功能损伤的作用。
将 50 只 Sprague-Dawley 大鼠随机分为 5 组（每组 10 只）：假手术组、CME 组、RES+CME 组、RES+CME+Sirtuin-1（SIRT-1）抑制剂 EX527（RES+CME+EX）组和 CME+EX 组。通过心脏超声、心肌酶评估、TdT 介导的 dUTP 末端标记和苏木精碱性品红-苦味酸染色测量心脏功能、血清 c-肌钙蛋白 I（cTnI）水平、凋亡指数和微梗死。通过 Western blot 检测 p53、p53 乙酰化、SIRT-1、Bax、Bcl-2 和 cleaved caspase-3 的水平。
CME 手术后出现心肌功能障碍、凋亡指数增加和 cTnI 升高。冠状动脉微栓塞诱导 p53 乙酰化和 cleaved caspase-3 表达增加，而 SIRT-1 和 Bcl-2/Bax 比值降低。RES 逆转了 CME 的作用，而 EX527 减弱了这种保护作用。
白藜芦醇可以改善心脏功能，减轻 CME 诱导的心肌细胞凋亡，这可能与其抑制 p53 促凋亡途径有关，该途径不依赖于转录。
