Trimetazidine Pretreatment Inhibits Myocardial Apoptosis and Improves Cardiac Function in a Swine Model of Coronary Microembolization
Trimetazidine Pretreatment Inhibits Myocardial Apoptosis and Improves Cardiac Function in a Swine Model of Coronary Microembolization
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DOI：
10.1159/000369246
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发表时间：
2015-01-01
期刊：
影响因子：
1.9
通讯作者：
Tang, Zhong-li
中科院分区：
文献类型：
--
作者：
Liu, Yang-Chun;Li, Lang;Tang, Zhong-li
目的：曲美他嗪（TMZ）是一种众所周知的抗缺血药物，但其对冠状动脉微栓塞（CME）的心脏保护作用及其机制尚不清楚。本研究旨在确定TMZ预处理是否能减轻CME猪模型的心肌细胞凋亡和改善心功能。方法：15只健康家猪随机分为假手术组、CME组和CME + TMZ组。通过向左前降支动脉注射惰性塑料微球（直径42 μ m）诱导CME。对照组注射等量生理盐水，TMZ组注射TMZ前30 min注射TMZ。术后12 h超声心动图检测心功能，TUNEL染色检测心肌细胞凋亡，Western blot检测caspase-9/3蛋白表达水平。结果如下：与对照组相比，CME组的心功能显著降低（p < 0.05）;然而，TMZ预处理显示与CME组相比心功能显著改善（p < 0.05）。CME组心肌细胞凋亡率和caspase-9/3表达水平均明显高于对照组（P < 0.001）。同样，TMZ预处理显著降低了凋亡率和切割的半胱天冬酶-9/3的表达水平（p < 0.001）。结论：TMZ预处理可明显抑制CME诱导的心肌细胞凋亡，改善心功能，其心肌保护作用可能与阻断线粒体凋亡途径有关。这些结果强调了TMZ预处理在CME诱导的心肌损伤治疗中的重要性。(C)2015 S. Karger AG，巴塞尔
Objective: Trimetazidine (TMZ) is a well-known anti-ischemic agent; however, its efficacy and mechanism of cardioprotection on coronary microembolization (CME) are largely unknown. The present study was undertaken to determine whether TMZ pretreatment could attenuate myocardial apoptosis and improve cardiac function in a swine model of CME. Methods: Fifteen swine were randomly and equally divided into a sham-operated (control) group, CME group and CME plus TMZ (TMZ) group. CME was induced by injecting inert plastic microspheres (42 mu m in diameter) into the left anterior descending artery. For the control group, the same dose of normal saline was substituted for the microspheres, and the TMZ group was pretreated with TMZ 30 min before microsphere injection. Cardiac function was assessed by echocardiography, myocardial apoptosis was detected by TUNEL staining, and the expression levels of cleaved caspase-9/3 were measured by Western blot 12 h after operation. Results: Compared to the control group, cardiac function in the CME group was significantly decreased (p < 0.05); however, TMZ pretreatment showed significantly improved cardiac function as compared to the CME group (p < 0.05). The myocardial apoptotic rate and the expression levels of cleaved caspase-9/3 increased remarkably in CME group as compared with the control group (p < 0.001). Again, TMZ pretreatment significantly reduced the apoptotic rate and also the expression levels of cleaved caspase-9/3 (p < 0.001). Condusion:The present study demonstrated that TMZ pretreatment could significantly inhibit CME-induced myocardial apoptosis and improve cardiac function, and that the cardioprotective effect appeared to be mediated by the blockade of the mitochondrial apoptotic pathway. These results emphasize the importance of TMZ pretreatment in the therapy of CME-induced myocardial injury. (C) 2015 S. Karger AG, Basel