曲美他嗪对吡喃阿霉素致心肌自由基损伤的保护作用

doi:10.13481/j.1671-587x.20140615

吉林大学学报(医学版)

曲美他嗪对吡喃阿霉素致心肌自由基损伤的保护作用

金菊香¹，陈海燕¹，李群²，李杰¹

1.吉林大学第一医院老年干部科，吉林长春 130021；2.吉林大学第一医院甲状腺外科，吉林长春 130021

收稿日期:2014-05-26 出版日期:2014-11-28 发布日期:2015-01-18
通讯作者: 李杰（Tel： 0431-88782272，E-mail：yabianwanghai@163.com） E-mail:yabianwanghai@163.com
作者简介:金菊香（1989-），女，吉林省龙井市人，在读医学硕士，主要从事心血管疾病临床与基础方面的研究。
基金资助:
吉林省科技厅自然科学基金资助课题（201015145）

Protective effect of trimetazidine on myocardial free radical injury induced by pirarubicin

JIN Ju-xiang¹,CHEN Hai-yan¹,LI Qun²,LI Jie¹

1.Department of Geratology,First Hospital，Jilin University,Changchun 130021，China；2. Department of Thyroid Surgery,First Hospital，Jilin University,Changchun 130021，China)

Received:2014-05-26 Online:2014-11-28 Published:2015-01-18

摘要/Abstract

摘要：

目的:探讨曲美他嗪（TMZ）对吡喃阿霉素（THP）致心肌自由基损伤的影响，阐明其对吡喃阿霉素致心肌损伤的保护作用及机制。方法：将36只Wistar大鼠随机分为吡喃阿霉素组13只、曲美他嗪干预组（THP+TMZ组)13只和正常对照组10只。吡喃阿霉素组和曲美他嗪干预组每周尾静脉注射吡喃阿霉素2.5 mg/kg，连续6周。曲美他嗪干预组于制备模型前1 d开始每日灌胃曲美他嗪5.4 mg/kg/d，喂养8周。实验结束时留取心肌组织行丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)和非蛋白巯基(NPSH)的测定，电镜观察心肌组织学变化。结果：与正常对照组比较，吡喃阿霉素组大鼠心肌组织中MDA及NO水平均升高（P<0.05），NPSH水平和SOD活性均降低（P<0.05）。与吡喃阿霉素组比较，曲美他嗪干预组大鼠心肌组织中MDA及NO水平均降低（P<0.05），NPSH水平和SOD活性均升高（P<0.05）。电镜下吡喃阿霉素组大鼠心肌细胞核呈不规则形，核基质呈空化状，周围胞质内肌丝束明显减少，肌节结构不清，闰盘结构隐约可见，线粒体明显肿胀；曲美他嗪干预组大鼠心肌细胞细胞核呈圆形，核基质略改变，肌丝束略减少，排列较整齐，闰盘结构仅局部不清，线粒体轻度肿胀。结论:曲美他嗪对吡喃阿霉素导致的心肌自由基损伤具有保护作用，可能与减少自由基产生，减轻细胞核、线粒体、闰盘等细胞结构的破坏有关。

关键词: 曲美他嗪；吡喃阿霉素；心肌细胞；线粒体, 自由基

Abstract:

Abstract:Objective To explore the effects of trimetazidine on myocardial free radical injury induced by pirarubicin， and to clarify the protective effect and mechanism of trimetazidine on myocardial injury induced by pirarubicin.Methods 36 Wistar rats were randomly divided into pirarubicin group（n=13），trimetazidine intervention group（n=13） and control group （n=10）.The rats in pirarubicin group and trimetazidine intervention group were injected with pirarubicin 2.5 mg/kg by the vena caudal once a week for 6 weeks.The rats in trimetazidine intervention group were intragastricly infused with trimetazidine 5.4 mg/kg/d one day for 8 weeks before making the model. At the end of the experiment,the malonaldehyde (MDA) level，nitrogen oxide（NO） level，superoxide dismutase(SOD) activity，and nonprotein sulfhydryl (NPSH) level in myocardium tissue were measured. The histological changes of myocardium tissue were detected by electron microscope. Results Compared with control group ,the levels of MDA and NO in pirarubicin group were increased（P<0.05），and the SOD activity and NPSH level in pirarubicin group were decreased（P<0.05）.Compared with pirarubicin group,the levels of MDA and NO in trimetazidine intervention group were decreased（P<0.05）， the SOD activity and NPSH level in trimetazidine intervention group were increased（P<0.05）.Under electron microscope,the myocardiocytes of the rats in pirarubicin group showed irregular arrangement in sacromere structure,shrinkage in nuclear membrane,vacuolation in nuclear matrix,obvious mitochondria swelling,deposition of metachromatin throughout the nucleus,and an indistinct view of intercalated disc with isolation;while in trimetazidine intervention group the nucleus was round and nuclear membrane was indented,myofilament bundles were decreased slightly with a regular arrangement，intercalated disc oriented transversely with partial vague in cell junction structure,and mitochondria slightly swelled.Conclusion Trimetazidine has the protective effects on the damaged myocardiocytes caused by pirarubicin,and its mechanism may be related to reducing the production of free radicals and decreasing the injury of structures within the cells,such as the nucleus,mitochondria and intercalated disc.

Key words: trimetazidine, pirarubicin, myocardiocytes;mitochondria, free radicals

中图分类号:

R965

. 曲美他嗪对吡喃阿霉素致心肌自由基损伤的保护作用[J]. 吉林大学学报(医学版), 2014, 40(06): 1197-1200.

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曲美他嗪对吡喃阿霉素致心肌自由基损伤的保护作用

Protective effect of trimetazidine on myocardial free radical injury induced by pirarubicin

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