羟氯喹对梗死区周边心肌共济失调毛细管扩张突变基因下游分子及凋亡的影响  

Effect of hydroxychloroquine on downstream proteins of ATM in myocardium and apoptosis of cardiomyocytes around the infarction zone in rats

作　　者：周婧[1] 李刚[1] 

机构地区：[1]重庆医科大学附属第一医院老年科心血管病组,重庆400016

出　　处：《临床心血管病杂志》2010年第5期375-377,共3页Journal of Clinical Cardiology

基　　金：重庆市科委自然科学基金[渝科发计字(2007)25号CSTC;2007BB5276];重庆市卫生局医学科学技术研究项目[渝卫教2004(53)04-2-154;2009-2-290]

摘　　要：目的:探讨羟氯喹对大鼠梗死区周边心肌共济失调毛细管扩张突变基因(ATM)下游信号分子及凋亡的影响。方法:按Maisel方法建立心肌梗死与假手术模型,将术后3 d仍存活的SD大鼠按不同干预条件分为心肌梗死羟氯喹组(A组,n=11),心肌梗死安慰剂组(B组,n=15),假手术羟氯喹组(C组,n=7),假手术安慰剂组(D组,n=7)。计算处理3个月后各组死亡率,原位TUNEL法检测心肌细胞凋亡,Western Blot测定梗死区周边心肌MMP-9、P-Akt、P53蛋白表达。结果:A、B、C、D组大鼠处理3个月后死亡率分别为9.0%、40.0%、0%、0%,心肌细胞凋亡率分别为(12±4)%、(30±5)%、(2±2)%、(3±2)%。A组与B组心肌MMP-9蛋白IA分别为0.67±0.11、1.07±0.13,P<0.05;P-Akt蛋白IA分别为1.12±0.21、0.58±0.18,P<0.05;P53蛋白IA分别为1.01±0.20、0.98±0.19,P>0.05。C组与D组心肌MMP-9蛋白IA分别为0.42±0.14、0.56±0.16,P>0.05;P-Akt蛋白IA分别为0.78±0.20、0.62±0.23,P>0.05;P53蛋白IA分别为0.49±0.22、0.32±0.19,P>0.05。结论:羟氯喹通过调控ATM的下游信号分子Akt蛋白表达及活性,可抑制梗死区周边心肌细胞凋亡,从而改善心肌梗死后心室重塑,降低死亡率。Objective：To investigate the effect of hydroxychloroquine on downstream protein of ataxia telangiectasia mutated（ATM） in myocardium and apoptosis of cardiomyocytes around the infarction zone in rats.Method：Myocardial infarction（MI） and sham-operation in rats were established by Maisel＇s method.Three days after operation,surviving Sprague-Dawley（SD） rats were divided into MI hydroxychloroquine group（n=11,group A）,MI placebo group（n=15,group B）,sham-operation hydroxychloroquine group（n=7,group C）,sham-operation placebo group（n=7,group D）,which were treated with hydroxychloroquine and physiological saline respectively.After three months treatment,mortality rate of rats in each group was calculated.Apoptosis of cardiomyocytes was observed by TdT-Mediated dUTP nick end labeling（TUNEL） in situ,and protein expression of MMP-9,P-Akt and P53 in myocardium around the infarction zone was detected by Western blot.Result：In group A,group B,group C,group D,Mortality rate of the rats was 9.0%,40.0%,0%,0% respectively,apoptosis rate of the myocardiocytes was（12±4）%,（30±5）%,（2±2）%,（3±2）%,respectively.In group A and group B myocardium,IA of MMP-9 was（0.67±0.11）,（1.07±0.13）,P〈0.05,respectively;IA of P-Akt was（1.12±0.21）,（0.58±0.18）,P〈0.05,respectively;IA of P53 was（1.01±0.20）,（0.98±0.19）,P〉0.05,respectively.In group C and group D myocardium,IA of MMP-9 was（0.42±0.14）,（0.56±0.16）,P〉0.05,respectively;IA of P-Akt was（0.78±0.20）,（0.62±0.23）,P〉0.05,respectively;IA of P53 was（0.49±0.22）,（0.32±0.19）,P〈0.05,respectively.Conclusion：By modulating the protein expression and activity of Akt,one of the downstream proteins of ATM,hydroxychloroquine can inhibit the apoptosis of myocardiocytes around the infarction zone.It＇s beneficial to preventing the postinfarciton ventricular remodeling,and reducing the mortality.

关 键 词：心肌梗死 凋亡 羟氯喹 共济失调毛细管扩张突变基因 

分 类 号：R542.2[医药卫生—心血管疾病]