Trimetazidine suppresses oxidative stress, inhibits MMP-2 and MMP-9 expression, and prevents cardiac rupture in mice with myocardial infarction
Trimetazidine suppresses oxidative stress, inhibits MMP-2 and MMP-9 expression, and prevents cardiac rupture in mice with myocardial infarction
复制标题
曲美他嗪抑制氧化应激，抑制MMP-2和MMP-9表达，预防心肌梗死小鼠心脏破裂
DOI：
10.1111/1755-5922.12460
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发表时间：
2018-10-01
影响因子：
3.1
通讯作者：
Nie, Shaoping
中科院分区：
文献类型：
--
作者：
Gong, Wei;Ma, Youcai;Nie, Shaoping
Background/AimsCardiac rupture (CR) is a catastrophic complication of acute myocardial infarction (MI). At present, there are no effective pharmacological strategies for preventing post-MI rupture. Here we investigated the effect of trimetazidine (TMZ) on post-MI CR.MethodsMI models were induced by left coronary artery ligation in male C57BL/6 mice. Animals allocated to the rupture incidence were closely monitored for 7days; autopsy was performed once animals were found dead to determine the reason of death. Heart function was detected by echocardiography. Oxidative stress markers and matrix metalloproteinases (MMPs) were analyzed by Western Blotting.ResultsTMZ markedly reduced the post-MI CR incidence of mice. We found that the expression of metalloproteinase (MMP) -2 and MMP-9 in the TMZ-treated group was significantly lower than the saline-treated group. Further, TMZ markedly attenuated MI-induced oxidative stress. To investigate the mechanism of the effect of TMZ on CR, we pretreated H9c2 cells with H2O2 and found that TMZ treatment markedly decreased H2O2-induced MMP-2 and MMP-9 expression. TMZ prevents CR through inhibition of oxidative stress, which is attributable to the down-regulation of MMP-2, MMP-9 expression.ConclusionsOur findings indicate that TMZ suppresses oxidative stress, inhibits MMP-2 and MMP-9 expression, and prevents CR in mice with MI.
