Paeoniflorin inhibits doxorubicin-induced cardiomyocyte apoptosis by downregulating microRNA-1 expression
Paeoniflorin inhibits doxorubicin-induced cardiomyocyte apoptosis by downregulating microRNA-1 expression
复制标题
芍药苷通过下调microRNA-1表达抑制阿霉素诱导的心肌细胞凋亡
DOI：
10.3892/etm.2016.3182
复制
发表时间：
2016-06-01
影响因子：
2.7
通讯作者：
Yang, Yang
中科院分区：
文献类型：
--
作者：
Li, Jian-Zhe;Tang, Xiu-Neng;Yang, Yang
阿霉素（DOX）是一种有效的蒽环类抗肿瘤抗生素。由于其心脏毒性，DOX的临床应用受到限制。芍药苷（PEF）是一种从芍药干根中提取的单萜苷，据报道对心血管系统有多种有益作用。本研究旨在探讨PEF对dox诱导的心肌细胞凋亡的保护作用及其机制。在培养的H9c2细胞中，在暴露于DOX (5 mu mol/l) 24小时之前，加入PEF (100 mu mol/l) 2小时。在PEF和/或DOX处理后，测量细胞活力、肌酸激酶活性、心肌细胞凋亡、细胞内活性氧（ROS）水平、microRNA-1 （miR-1）和b细胞淋巴瘤2 （Bcl-2）的表达。结果显示，DOX显著诱导心肌细胞凋亡，同时ROS生成增强，miR-1表达上调，Bcl-2表达下调。经PEF预处理后，DOX的这些作用被显著抑制。这些结果表明，PEF对dox诱导的心肌细胞凋亡的抑制作用可能与通过减少ROS生成下调miR-1表达有关。
Doxorubicin (DOX) is an effective anthracycline anti-tumor antibiotic. Because of its cardiotoxicity, the clinical application of DOX is limited. Paeoniflorin (PEF), a monoterpene glucoside extracted from the dry root of Paeonia, is reported to exert multiple beneficial effects on the cardiovascular system. The present study was designed to explore the protective effect of PEF against DOX-induced cardiomyocyte apoptosis and the underlying mechanism. In cultured H9c2 cells, PEF (100 mu mol/l) was added for 2 h prior to exposure to DOX (5 mu mol/l) for 24 h. Cell viability, creatine kinase activity, cardiomyocyte apoptosis, intracellular reactive oxygen species (ROS) levels, and the expression of microRNA-1 (miR-1) and B-cell lymphoma 2 (Bcl-2) were measured following treatment with PEF and/or DOX. The results showed that treatment with DOX notably induced cardiomyocyte apoptosis, concomitantly with enhanced ROS generation, upregulated miR-1 expression and downregulated Bcl-2 expression. These effects of DOX were significantly inhibited by pretreatment of the cells with PEF. These results suggest that the inhibitory effect of PEF on DOX-induced cardiomyocyte apoptosis may be associated with downregulation of miR-1 expression via a reduction in ROS generation.