曲美他嗪对急性心肌梗死大鼠心室重构的抑制作用

发布时间：2018-03-18 06:17

本文选题：曲美他嗪　切入点：急性心肌梗死　出处：《中国老年学杂志》2016年20期 　论文类型：期刊论文

【摘要】：目的探讨曲美他嗪对急性心肌梗死(AMI)大鼠心室重构的抑制作用及其可能机制。方法取清洁级雄性健康SD大鼠60只,随机数字表法随机分为4组,每组各15只,即假手术组(C组),AMI模型组(M组),曲美他嗪低剂量组(L组),曲美他嗪高剂量组(H组)。C组只穿线不结扎,M、L、H三组均行开胸结扎左冠脉前降支方案,构建大鼠AMI模型,术后12 h开始L、H组分别给予曲美他嗪相应剂量灌胃1次/d(L组10 mg·kg~(-1)·d~(-1),H组20 mg·kg~(-1)·d~(-1)),喂养4 w。各组分别于术后24 h于眼动脉取血2 ml,测定血清肌酸激酶(CPK),丙二醛(MDA),超氧化物歧化酶(T-SOD),游离脂肪酸(FFA)。术后4 w观察各组心肌肥厚指数变化和各组心肌胶原(MC)含量变化,获取心肌细胞结构及心肌胶原纤维增生的有关图像数据。结果术后24 h各组血清CPK、血清MDA均较C组升高(P均0.05),而血清T-SOD较C组则下降(P均0.05),其中M组变化最显著;L、H组血清CPK、血清MDA较M组减低,而血清T-SOD则升高(P均0.05),且H组变化更为显著(P0.05)。另外,M组血清FFA较C组显著升高(P0.05),L、H组较M组则显著降低(P0.05)。术后4 w,与C组比较,M、L、H组心肌肥厚指数均增大(P均0.01),而M组增大最明显;与M组比较,L、H组则明显下降(P0.05)。术后4 w,与C组比较,M、L、H组MC含量均明显升高(P均0.05),而M组升高最显著(P0.001),与M组比较,L、H组则显著下降(P0.05),且呈剂量依赖性。MC含量与血清CPK活力(r=0.85,P0.001)和MDA含量(r=0.76,P0.001)呈正相关。光镜MASSON染色和透射电镜结果显示:M组心肌及线粒体结构破坏最严重,且胶原纤维堆积明显,L、H组较M组改善。结论曲美他嗪对大鼠AMI后心室重构有抑制效果,缓解心肌纤维化。且这可能与其优化心肌代谢、减轻细胞缺血损伤后氧化应激反应、保护线粒体超微结构从而减少心肌细胞损伤作用相关。
[Abstract]:Objective to investigate the inhibitory effect of trimetazidine on ventricular remodeling in acute myocardial infarction (AMI) rats and its possible mechanism. Methods Sixty healthy male SD rats of clean grade were randomly divided into 4 groups with 15 rats in each group. The AMI model of rats was established by opening thoracic ligation of left anterior descending coronary artery in group C, low dose trimetazidine group, trimetazidine high dose group, and trimetazidine high dose group H group and without ligation of left anterior coronary artery descending branch, all of the three groups were treated with open chest ligation of left anterior descending coronary artery. From 12 h after operation, the Lon H group was given trimetazidine at a dose of 10 mg 路kg -1) 路dron-1g / L group (n = 10 mg 路kg ~ (-1)) 路D ~ (2 +) 路L ~ (-1) / L group respectively, and fed with 20 mg 路kg ~ (-1) 路d ~ (-1) of trimetazidine for 4 weeks. The blood samples were taken from the ophthalmic artery at 24 h after operation, and the serum creatine kinase (CPK), malondialdehyde (MDA) MDAA, superoxide dismutase (SOD) were measured. The changes of myocardial hypertrophy index and myocardial collagen content in each group were observed 4 weeks after operation. Results 24 hours after operation, the serum CPKs and serum MDA levels in each group were higher than those in group C (P 0.05), while serum T-SOD was lower than that in group C (P 0.05), especially in group M (P < 0.05). The levels of serum CPK and serum MDA were significantly lower in group C than in group M. In addition, the serum FFA in group M was significantly higher than that in group C (P 0.05). The serum level of T-SOD in group M was significantly lower than that in group M at 4 weeks after operation. Compared with group C, the myocardial hypertrophy index in group C was increased (P < 0.01), while that in group M was the most significant. After 4 weeks of operation, compared with group C, the content of MC in group M was significantly higher than that in group C (P 0.05), while that in group M was significantly higher than that in group M (P 0.001). Compared with that in group M, the content of MC in group C was significantly lower than that in group M, and the content of MC in serum was in a dose-dependent manner. There was a positive correlation between the activity of CPK and the content of MDA. The results of MASSON staining and transmission electron microscopy showed that the damage of myocardial and mitochondrial structures was the most serious in group M. Conclusion trimetazidine can inhibit ventricular remodeling and alleviate myocardial fibrosis after AMI in rats. The protection of mitochondrial ultrastructure to reduce myocardial cell injury is related to.
【作者单位】：河北医科大学唐山临床学院唐山市工人医院心内一科;
【基金】：2015年度河北省医学科学研究重点课题(No.ZL20140252)
【分类号】：R542.22

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