Ma Ning, Bai Jingyun, Zhang Weihua, Luo Hong, Zhang Xin, Liu Donghai, Qiao Chenhui
Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4216-4222. doi: 10.3892/mmr.2016.5773. Epub 2016 Sep 26.
Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)‑21 expression, Akt, and the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA‑21, Bcl‑2, Bax and phosphorylated‑Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA‑21 expression and phosphorylated‑Akt protein expression, and reduced the Bcl‑2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA‑21 using anti‑miR‑21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA‑21 serves a protective role in cardiac I/R injury via Akt and the Bcl‑2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA‑21 expression, Akt, and the Bcl‑2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA‑21 on cardiac I/R injury following treatment with trimetazidine in vivo.
曲美他嗪是一种哌嗪衍生的代谢剂,具有细胞保护作用,据报道对慢性稳定型心绞痛有效。此外,它还被证明对急性心肌梗死有保护作用。本研究旨在探讨曲美他嗪是否能预防心脏缺血/再缺血/再灌注(I/R)损伤,并确定其疗效是否与微小RNA(miRNA)-21表达、Akt以及B细胞淋巴瘤2(Bcl-2)/Bcl-2相关X蛋白(Bax)途径有关。通过结扎成年大鼠左冠状动脉前降支诱导心脏I/R损伤。随后,评估心脏功能,并使用定量聚合酶链反应和蛋白质印迹法检测miRNA-21、Bcl-2、Bax和磷酸化Akt的表达水平。结果表明,曲美他嗪能够显著保护心脏功能,并减少大鼠心脏I/R损伤后的梗死面积。此外,曲美他嗪显著促进心脏I/R损伤大鼠的miRNA-21表达和磷酸化Akt蛋白表达,并降低Bcl-2/Bax比值。使用抗miR-21质粒敲低miRNA-21能够逆转曲美他嗪对心脏I/R损伤的保护作用。这些结果表明,miRNA-21通过Akt和Bcl-2/Bax途径在心脏I/R损伤中发挥保护作用。此外,曲美他嗪通过心脏miRNA-21表达、Akt和Bcl-2/Bax途径对心脏I/R损伤发挥保护作用。因此,本研究为曲美他嗪体内治疗后miRNA-21对心脏I/R损伤的保护作用提供了证据。