曲美他嗪对吡喃阿霉素致大鼠心肌结构损伤的保护作用及其机制  

Protective effects of trimetazidine on myocardial structure injury induced by pyran adriamycin and its mechanism

作　　者：邵明柏[1] 陈海燕[1] 李群[2] 李杰[1] 

机构地区：[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

出　　处：《吉林大学学报（医学版）》2014年第4期816-819,I0003,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅自然科学基金资助课题(201015145)

摘　　要：目的:探讨曲美他嗪对吡喃阿霉素致大鼠心肌结构改变的影响,阐明曲美他嗪对大鼠心肌结构改变的保护作用及其机制。方法:36只Wistar大鼠随机分为空白组、模型组和用药组,模型组和用药组大鼠每周尾静脉注射吡喃阿霉素(2g·L-1)2.5mg·kg-1,空白组大鼠给予尾静脉注射等量生理盐水,连续6周;用药组大鼠于造模前1d开始每日灌胃曲美他嗪5.4mg·kg-1,空白组和模型组大鼠灌胃等量生理盐水,喂养8周。实验结束时检测各组大鼠血清心肌酶学指标;留取大鼠心肌组织,采用光镜和电镜观察组织形态学表现。结果:与对照组比较,模型组大鼠血清肌红蛋白、肌钙蛋白I和丙氨酸氨基转移酶(ALT)均升高(P<0.05),用药组仅肌钙蛋白I升高(P<0.05),肌红蛋白和ALT差异无统计学意义(P>0.05)。与模型组比较,用药组大鼠血清肌红蛋白、肌钙蛋白I和ALT水平明显降低(P<0.05)。光镜下观察,模型组大鼠心肌排列紊乱,结构严重受损,多处可见心肌溶解,肌丝断裂;用药组大鼠心肌结构基本完整,局部有溶解、断裂,程度较模型组减轻。电镜下观察,模型组大鼠心肌细胞肌丝束溶解、断裂、消失,线粒体减少,胞质基质空化;用药组大鼠心肌细胞肌丝束肌节结构排列整齐,局部肌丝略有减少,周围线粒体呈椭圆形,平行排列于肌丝束之间。结论:曲美他嗪对吡喃阿霉素导致的心肌细胞损伤具有保护作用,其作用机制可能与减少线粒体损伤和细胞破坏有关。Objective To explore the effect of trimetazidine on myocardial structure injury induced by pyran adriamycin and to clarify the protective effect of trimetazidine on.the changes of myocardial structure and its mechanism.Methods 36Wistar rats were randomly divided into control group,model group and treatment group.The rats in model group and treatment group were injected with pyran doxorubicin 2.5mg·kg^-1（concentration2g·L^-1）by the caudal vein once a week.The rats in control group were injected with equivalent normal saline for6weeks.The rats in treatment group were intragastricly infused with trimetazidine 5.4 mg·kg·d-1 one day before making the model.The rats in control group and model group were injected with equivalent normal saline for8weeks.At the end of the experiment,the myocardial enzymes in serum of the rats in various groups were measured.The morphology of myocardium tissue was detected by light microscope and electron microscope.Results Compared with model group,the levels of myoglobin,troponin I and alanine transaminase（ALT）of the rats in treatment group were significantly decreased（P〈0.05）.Under light microscope the myocardium of the rats in model group arranged disorderly,the structure was severely damaged,emyocardial was seen,the myofilament was dissolved;the myocardium of the rats in treatment group arranged in order,the structure was nearly integrated,partial dissolution and fracture were found.Under electron microscope in model group the myocardial muscle bundle dissolved,fractured and disappeared,and the mitochondria was decreased,and the cytoplasmic matrix cavitation was seen;the cardiomyocytes sarcomeres of the rats in treatment group arranged in order,local myofilaments were reduced slightly,the surrounding mitochondria were oval and arranged in parallel between the muscle bundles.Conclusion Trimetazidine has protective effect on the cardiomyocyte injury caused by pyran adriamycin,and its mechanism may be related to decreasing the injury of mitochondria and myocytes.

关 键 词：曲美他嗪 吡喃阿霉素 线粒体 心肌酶 心肌结构 

分 类 号：R332[医药卫生—人体生理学] R365.54[医药卫生—基础医学]