曲美他嗪影响巴马小型猪冠状动脉微栓塞后心肌细胞凋亡的机制
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国家自然科学基金资助项目(81260042)


Effect of Pretreatment with Trimetazidine on Cardiomyocyte Apoptosis After Coronary Microembolization in Swine
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    摘要:

    目的 探讨曲美他嗪对巴马系小型猪急性冠状动脉微栓塞(CME)后心肌细胞凋亡的影响及意义。方法 健康巴马系小型猪随机分为假手术组、CME组和CME+曲美他嗪组,每组5只。采用经皮冠状动脉介入法,于左前降支中远端经微导管注入微栓塞球建立CME模型;假手术组注入等量生理盐水;CME+曲美他嗪组术前30 min经耳缘静脉注入曲美他嗪。术后9 h采用心脏超声检测心功能,TUNEL染色检测心肌细胞凋亡,Western blot检测活化Caspase-8和Caspase-3表达水平。结果 与假手术组相比,CME组左心室射血分数(LVEF)、左心室短轴缩短率(FS)及心排血量(CO)下降,左心室舒张期末内径(LVEDd)增加(P<0.05);与CME组相比,CME+曲美他嗪组心功能明显改善(P<0.05)。与假手术组相比,CME组心肌细胞凋亡率、活化Caspase-8及Caspase-3含量显著增加(P<0.05);与CME组相比,CME+曲美他嗪组心肌细胞凋亡率、活化Caspae-8及Caspase-3含量明显减少(P<0.05)。结论 曲美他嗪预处理可明显减少CME后心肌细胞凋亡并改善心功能,其机制可能是阻断心肌细胞Caspase-8介导的死亡受体凋亡途径的激活。

    Abstract:

    Aim To explore the effect of trimetazidine on cardiomyocyte apoptosis after coronary microembolization (CME) in swine. Methods Fifteen swine were randomly and equally assigned into sham-operated (control) group,CME group and trimetazidine group.CME was induced by injection of microspheres selectively into left anterior descending artery for control group,the same dose of normal saline was substituted for microspheres and those in trimetazidine group were pretreated with trimetazidine 30 min before microspheres injection.Cardiac function was assessed by echocardiography,cardiomyocyte apoptosis was detected by TUNEL staining,and the expression levels of caspase-8 and caspase-3 were measured by Western blot 9 h after operation. Results Compared with sham-operated group,cardiac function was significantly decreased in CME group (P<0.05) However,cardiac function was significantly improved in trimetazidine group compared with CME group (P<0.05).Compared with control group,myocardial apoptosis rate and the levels of activated caspase-8 and -3 increased significantly in CME group (P<0.05).Again,these effects were ameliorated by trimetazidine (P<0.05). Conclusion Trimetazidine pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function probably by inhibiting myocardial death receptor-mediated apoptotic pathway.

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刘阳春,李 浪,苏 强,刘 涛,麻芝英,王现涛.曲美他嗪影响巴马小型猪冠状动脉微栓塞后心肌细胞凋亡的机制[J].中国动脉硬化杂志,2015,23(07):657~662.

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  • 收稿日期:2014-07-10
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  • 在线发布日期: 2015-07-03