曲美他嗪
活力测定
胱硫醚γ裂解酶
氧化应激
药理学
乳酸脱氢酶
胱硫醚β合酶
细胞凋亡
下调和上调
缺氧(环境)
心肌保护
活性氧
医学
化学
生物化学
缺血
内科学
酶
氧气
半胱氨酸
有机化学
基因
作者
Wenqing Zheng,Chao Liu
标识
DOI:10.14744/anatoljcardiol.2019.83648
摘要
Trimetazidine is a piperazine-derived metabolic agent. It exerts cardioprotective effects against myocardial ischemia/reperfusion (I/R) injury. In addition, studies confirm that the cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway serves a beneficent role in attenuating myocardial I/R injury. However, the underlying role of the CSE/H2S pathway in the trimetazidine-induced protection against myocardial I/R injury remains elusive. Therefore, this study investigated whether trimetazidine ameliorates hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injuries in an in vitro cell model of myocardial I/R injury, by enhancing the CSE/H2S pathway.The H9c2 cell viability was determined with a cell counting Kit-8.Trimetazidine significantly increased the cell viability and decreased lactate dehydrogenase (LDH) release in H/R-treated H9c2 cells. Additionally, trimetazidine increased the H2S levels and the CSE mRNA and protein levels, promoting the CSE/H2S pathway under H/R conditions. The inhibition of the CSE/H2S pathway, induced by transfection with specific siRNA against human CSE (si-CSE), eliminated the trimetazidine-induced upregulation of cell viability, downregulation of LDH release, increase of caspase-3 activity and apoptosis regulator BAX expression, and the decrease of apoptosis regulator Bcl-2 expression, which suggests involvement of the CSE/H2S pathway in trimetazidine-induced cardioprotection. Furthermore, trimetazidine mitigated the H/R-induced increase in reactive oxygen species production and NADPH oxidase 2 expression, and decrease in superoxide dismutase activity and glutathione level, in H9c2 cells. These effects were also reversed by si-CSE.This study revealed that the CSE/H2S pathway mediates the trimetazidine-induced protection of H9c2 cardiomyocytes against H/R-induced damage by inhibiting apoptosis and oxidative stress.
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