吉林大学学报(医学版)

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阿托伐他汀对心肌缺血再灌注损伤大鼠心肌酶和心肌细胞凋亡的影响及其心肌保护作用机制

黄可欣1, 石博1, 叶保国2, 宋雪松2   

  1. 1.吉林大学白求恩医学院形态学中心，吉林 长春 130021；2. 吉林大学第一医院麻醉科，吉林 长春 130021
  • 收稿日期:2013-04-15 出版日期:2013-09-28 发布日期:2013-12-13
  • 通讯作者: 宋雪松（Tel:0431-88782563,E-mail:songxs@jlu.edu.cn） E-mail:songxs@jlu.edu.cn
  • 作者简介:黄可欣（1974-），女，吉林省白山市人，实验师，医学硕士，主要从事细胞免疫学的研究。
  • 基金资助:

     吉林省教育厅科研基金资助课题（2010268）

Effects of atorvastatin on myocardial enzymes and apoptosis in rat with myocardial ischemia-reperfusion injuryand mechanism of its protection on myocardium

HUANG Ke-xin1,SHI Bo1,YE Bao-guo2,SONG Xue-song2   

  1. 1.Morphology Center,Norman Bethune College of Medicine,Jilin University,Changchun 130021,China；2. Department of Anesthesiology,First Hospital,Jilin University,Changchun 130021,China
  • Received:2013-04-15 Online:2013-09-28 Published:2013-12-13

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摘要：

［摘 要］ 目的：探讨阿托伐他汀(AT)对心肌缺血再灌注（I/R）损伤大鼠心肌酶及心肌细胞凋亡的影响，阐明AT对I/R大鼠心肌组织的保护作用机制。方法：健康雄性Wistar大鼠80只，3月龄，随机分为假手术组(S组)、I/R组、大剂量AT组(LAT组，10 mg/kg)和小剂量AT组(SAT组，1 mg/kg) ，每组20只。采用结扎左冠状动脉前降支(LAD)的方法制备I/R模型；采用生物化学方法检测大鼠血清中磷酸肌酸激酶(CK)、乳酸脱氢酶(LDH)、丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)及谷胱甘肽(GSH)的水平；采用免疫组织化学方法检测大鼠心肌组织中Fas、Bax及Bcl-2蛋白的表达水平。结果：生物化学方法检测，与S组比较，I/R组大鼠血清CK、LDH和MDA水平升高(P<0.01)，NO、SOD、GSH-Px和GSH水平降低(P<0.01)；与I/R组比较，LAT组和SAT组CK活性、LDH及血清MDA水平明显降低(P<0.01)，血清NO水平、SOD、GSH-Px及GSH水平明显升高(P<0.01)，LAT组和SAT组各项指标组间比较差异无统计学意义(P>0.05)；免疫组织化学方法检测，与S组比较，I/R组、LAT组和SAT组大鼠心肌组织Fas和Bax蛋白的表达水平均显著升高(P<0.01)；与I/R组比较，LAT组和SAT组大鼠心肌组织Fas蛋白的表达水平均显著降低(P<0.01)，LAT组和SAT组大鼠心肌组织Bax蛋白的表达水平与I/R组比较差异无统计学意义(P>0.05)；与S组比较，I/R组、LAT组和SAT组大鼠心肌组织Bcl-2蛋白的表达水平均升高，其中LAT组大鼠心肌组织Bcl-2蛋白的表达水平与S组比较差异有统计学意义(P<0.01)，而其他各组间比较差异无统计学意义(P>0.05)。结论：AT对I/R模型大鼠心肌组织具有保护作用，可能与减轻心肌酶学的改变、抑制Fas蛋白的表达及促进Bcl-2蛋白的表达有关。

关键词: 心肌缺血再灌注, 阿托伐他汀, 心肌酶, 载脂蛋白, Bcl-2蛋白, Bax蛋白

Abstract:

Abstract:Objective To explore the effects of atorvastatin(AT) on myocardial enzymes and apoptosis of myocardial cells in rats with myocardial ischemia reperfusion (I/R) injury and to clarify the mechanism of protective effect of AT on I/R rat myocardium tissue.Methods 80 healthy male Wistar rats,3 months old,were randomly divided into  sham operation(S) group,ischemia reperfusion(I/R) group,large dose AT group (LAT group,10 mg/kg) and small dose AT group (SAT group,1 mg/kg)(n=20).I/R model was prepared by ligating the coronary artery of the left anterior descending artery(LAD).The biochemical methods were used to detect the contents of serum creatine kinase(CK),lactate dehydrogenase(LDH),malondialdehyde(MDA),nitric oxide(NO),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px) and glutathione(GSH) in myocardium tissue;the immunohistochemical methods were used to detect the expressions of Fas,Bax and Bcl-2 proteins in myocardium tissue.Results Compared with S group,the  myocardial CK,LDH,MAD activities of the rats in I/R group were increased(P<0.01), and the NO,SOD,GSH-Px,GSH activities were decreased(P<0.01).Compared with I/R group,the CK activities,LDH activities and serum MDA activities  in LAT and SAT groups were reduced (P<0.01);and the levels of serum NO,serum SOD activities,GSH-Px activities and GSH contents were increased(P<0.01),but there was no significant difference between LAT group and SAT group (P>0.05).Compared with S group, the Fas and of Bax expressions in myocardium tissue in I/R group,LAT group and SAT group were significantly increased (P<0.01).Compared with  I/R group,the Fas  protein expression in rat myocardium tissue in LAT and SAT groups were significantly reduced(P<0.01);but the expression of Bax  protein had no significant difference between LAT group,SAT group and I/R group (P>0.05).Compared with S group,the Bcl-2  protein expressions in I/R group,LAT group,and SAT group were increased,and there was significant difference between LAT group and S group (P<0.01),while the difference was not statistically significant(P>0.05) among the other groups.Conclusion AT has protective effect on myocardium tissue of the rats with myocardial  I/R injury,and its mechanism may be related to reducing the changes of myocardia enzymes and inhibiting the protein expression of Fas  and promoting the expression of Bcl-2  protein.

Key words: myocardial ischemia reperfusion, atorvastatin, myocardial enzymes, apolipoprotein, Bcl-2 protein, Bax protein

中图分类号: 

  • R543.5
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