曲美他嗪对心肌梗死大鼠心肌细胞凋亡和自噬及心功能的影响

Effects of trimetazidine on cardiomyocyte apoptosis, autophagy and cardiac function in rats with myocardial infarction

目的:观察曲美他嗪对心肌梗死模型大鼠缺血心肌细胞凋亡、自噬以及心功能的影响。方法:成年雄性,SD大鼠,SPF级,90只,随机分为假手术组、模型对照组和曲美他嗪干预组,假手术组暴露心脏后不结扎前降支,模型对照组结扎前降支,曲美他嗪干预组结扎前降支后给予10 mg·kg^-1·d^-1曲美他嗪,连续4周。心肌细胞凋亡使用TUNEL法检测,LC3Ⅱ自噬蛋白使用Western blot检测。Vevo2100小动物超声仪测定LVESD、短轴缩短分数(FS)和EF。结果:HE病理切片显示曲美他嗪干预心肌细胞坏死和间质炎性细胞浸润较模型对照组减轻。模型对照组心肌凋亡指数为(20.87±5.64)%,显著高于曲美他嗪干预组的[(10.26±1.88)%,P<0.01]。曲美他嗪干预组心肌凋亡指数显著高于假手术组的[(0.62±0.14)%,P<0.01]。假手术组、模型对照组和曲美他嗪干预组心肌自噬蛋白LC3Ⅱ相对灰度值分别为[(0.13±0.02)vs.(0.42±0.09)vs.(0.73±0.14),P<0.01]。假手术组心肌自噬蛋白LC3Ⅱ表达显著低于模型对照组,模型对照组又显著低于曲美他嗪干预组。术后4周,曲美他嗪干预组LVEDD显著低于模型对照组(P<0.05),而FS和EF又显著高于模型对照组(P<0.05)。结论:曲美他嗪显著减低心肌梗死模型大鼠心肌细胞凋亡和增加心肌细胞自噬,有利于心功能的恢复。

Objective:To detect the effects of trimetazidine on cardiomyocyte apoptosis,autophagy and cardiac functionin in rats with myocardial infarction.Methods:ninety SPF-grade adult male SDs were randomly divided into sham-operated group,control model group and trimetazidine model group.The anterior descending artery was not ligated in sham operation group,ligated in control model group,ligated and given trimetazidine(10 mg·kg^-1·d^-1 for 4 weeks)in trimetazidine model group.TUNEL was used to detect cardiomyocyte apoptosis.LC3Ⅱprotein was detected by Western blot.LVESD,FS,and ES was detected by Vevo2100 ultrasound.Results:The myocardial necrosis and interstitial inflammatory cell infiltration was reduced in trimetazidine model group by HE staining,compared with control model group.The index of myocardial apoptosis in control model group was(20.87±5.64)%,which was significantly higher than that of(10.26±1.88)%in trimetazidine model group(P<0.01).The relative gray values of LC3 II in sham operation group,control model group and trimetazidine model group was 0.13±0.02,0.42±0.09,and 0.73±0.14.There was significant difference among the three groups(P<0.01).LC3Ⅱwas lower in control model group than that in trimetazidine model group.LVEDD in trimetazidine model group was significantly lower than that in control model group(P<0.05),while FS and EF in trimetazidine model group were significantly higher than that in control model group at postoperative 4 weeks(P<0.05).Conclusions:Trimetazidine can significantly reduce myocardial apoptosis and increase myocardial autophagy in rats with myocardial infarction,which is beneficial to the recovery of cardiac function.