曲美他嗪后处理对心肌缺血再灌注损伤大鼠细胞凋亡的保护性作用

Trimetazidine post-conditioning protects rats from cardiocyte apoptosis after myocardial ischemia/reperfusion injury

摘要:

目的 研究曲美他嗪后处理对大鼠急性心肌缺血再灌注损伤后细胞凋亡的影响。方法 实验大鼠40只，随机分为5组：假手术组（n＝8）、再灌注损伤模型组（n＝8）、曲美他嗪低剂量组（10mg/kg，n＝8）、曲美他嗪高剂量组（20mg/kg，n＝8），后处理组（n＝8）。制作再灌注损伤模型后，观察各组大鼠心肌梗死面积、Bcl2/bax蛋白表达以及电子显微镜下心肌组织切片观察。结果 （1）各组大鼠心肌梗死面积测定：假手术组未见梗死，其余各组大鼠心肌组织不同程度梗死，以后处理组及曲美他嗪高剂量组最轻，差异具有统计学意义（P＜0.01）。（2）各组大鼠Bcl2/Bax蛋白表达比较：在模型组中Bax蛋白强阳性表达，表现为软件分析结果灰度值最低。而曲美他嗪高剂量组及后处理组灰度值较模型组比较灰度值明显增大（P＜0.01）。Bcl2蛋白在模型组中表达较少，在曲美他嗪高剂量组中及后处理组中明显表达，且差异具有统计学意义（P＜0.01）。（3）电子显微镜下观察：除假手术组大鼠外，各组大鼠均有不同程度损伤及细胞凋亡，后处理组及曲美他嗪高剂量组损伤较轻。结论 高剂量曲美他嗪（20mg/kg）对大鼠心肌缺血再灌注损伤后细胞凋亡有抑制作用。

Abstract:

Objective To determine the protective effect of trimetazidine post-conditioning on cell apoptosis in rats induced by myocardial ischemia/reperfusion injury (MIRI). Methods Forty healthy adult Wistar rats were randomly assigned to sham-operation group, MIRI group, ischemic post-conditioning group and two trimetazidinee treatment groups (10 and 20mg/kg), with 8 rats in each group. MIRI model was established by ligation of coronary artery for 30min followed by 120min reperfusion. The rats in ischemic post-conditioning group were given another three times of ischemia/reperfusion for 30s at the interval of 30min ischemia and 120min reperfusion. Trimetazidinee or normal saline at same volume was given intragastrically to corresponding rats during the 30min ischemia. After MIRI, myocardial infarct area was measured, the expression of Bcl2 and bax was detected by immunohistochemical assays, and the myocardiocyte ultrastructure was observed with transmission electron microscopy. Results (1) Myocardial infarct area. No infarct was seen in the sham-operation group, but infarcts with different severities were found in the other groups, with those in the ischemic post-conditioning group and 20mg/kg trimetazidinee treatment group mildest (P＜0.01). (2) The expression of Bcl2/bax protein. The expression of Bax was very strong, while that of Bcl2 was very weak in the MIRI group, when compared with 20mg/kg trimetazidine group and ischemic post-conditioning group (both P＜0.01). (3) Morphology of cardiac muscle. Besides sham-operation group, ischemia/reperfusion injury and cardiocyte apoptosis were observed in other groups, with those in the ischemic post-conditioning group and 20mg/kg trimetazidinee treatment group most mildly. Conclusion Trimetazidine of 20mg/kg inhibits cardiocyte apoptosis in rats after MIRI.