阿托伐他汀对小鼠病毒性心肌炎心肌细胞凋亡的影响研究  

Atorvastatin Inhibits Cardiomyocyte Apoptosis in Viral Myocarditis Mice

作　　者：关键[1] 孙妍[2] 孙筱璐[1] 梁岩[1] 王国干[1] 

机构地区：[1]中国医学科学院北京协和医学院心血管病研究所阜外心血管病医院心内科,北京市100037 [2]北京煤炭总医院心脏中心

出　　处：《中国循环杂志》2011年第3期220-223,共4页Chinese Circulation Journal

基　　金：国家博士点基金资助(2006-GB05)

摘　　要：目的:阿托伐他汀钙(atorvastatin)对减少小鼠病毒性心肌炎(VMC)心肌细胞凋亡的影响。方法:4周龄小鼠146只按随机数字法分为4组:正常对照组(正常组,n=18);病毒性心肌炎组(VMC组,n=60);阿托伐他汀钙药物对照组(对照组,n=18);阿托伐他汀钙治疗病毒性心肌炎组(VMC药物治疗组,n=50)。VMC组及VMC药物治疗组小鼠腹腔接种柯萨奇病毒,正常组及对照组未注射病毒,VMC组及VMC药物治疗组小鼠给予阿托伐他汀钙,连续用药2周。用药后3、7、10、14、21、30天,苏木素-伊红染色观察心肌组织炎症浸润程度,电镜观察心肌胶原纤维及各种细胞器的变化。缺口末端标记法(TUNEL)检测心肌细胞凋亡情况。反转录酶-聚合酶连锁反应(RT-PCR)及蛋白质印迹方法检测心肌脂肪酸合成酶(Fas)信使核糖核酸(mRNA)和蛋白的表达水平。结果:VMC组比VMC药物治疗组的30天累计生存率低,差异有统计学意义(P=0.008)。VMC药物冶疗组比VMC组在第10、14、21、30天的心肌病理组织学积分均减少,差异有统计学意义(P<0.05)。VMC药物治疗组比VMC组心肌损伤的病灶数量少,心肌线粒体和肌浆网改变也较同期VMC组轻。第14、21天VMC药物治疗组比VMC组凋亡指数降低,差异有统计学意义(P<0.05)。VMC组比正常组Fas mRNA和蛋白的表达均增加,VMC药物治疗组比VMC组FasmRNA和蛋白的表达均减少,差异有统计学意义(P<0.05)。结论:阿托伐他汀钙改善VMC小鼠生存率,改善组织病理学表现,其机制可能与通过下调Fas转录及表达,从而抑制心肌细胞凋亡有关。表明阿托伐他汀钙对VMC小鼠有明显的保护作用。Objective ：To investigate the inhibition effect of atorvastatin on cardiomyocyte apoptosis in viral myocarditis（ VMC）mice. Methods：The VMC model was induced by Coxsakie virus B3 injection,and the mice were divided into four groups. Normal control group,n= 18 ,VMC group, n= 60, Atorvastatin control group, n = 18, in which the mice were treated with Atorvastatin, and VMC＋Atorvastatin group,n = 50. The animals received Atorvastatin 3 days after virus injection and the medication lasted for 2 weeks. 3,7,10,14,21, and 30 days after the medication, the myocardial inflammation was examined by histochemistry staining,the cardiomyocyte apoptosis was determined by TdT-mediated Dutp nick end labeling （TUNEL）method, fatty acid synthase （FAS） mRNA and protein expression were detected by RT-PCR and western blot analysis respectively. Results：Compared with VMC group,the 30 days survival rate was higher in VMG＋ Atorvastatin group,it also presented the improved the pathological features at 10,14,21 and 30 days after the medication,TUNEL indicated that the cardiomyocyte apoptosis was much flower in VMC ＋Atorvastatin group at 14 and 27 days after the roedication,P 〈0.05 respeetively. RT-PCR and westem blot analysis revealed that the FAS mRNA and protein expression were both increased in VMC group than that in Normal control group,were both decreased in VMC＋Atorvastatin group than that in VMC group,P〈0. 05 respectively. Conclusion ： Atorvastatin improves the survival rate and the pathological features in VMC mice, which might be because of the down regulation of Fas expression and therefore,inhibit the cardiomyocyte apoptosis.

关 键 词：病毒性心肌炎 阿托伐他汀钙 凋亡 心肌脂肪酸合成酶 

分 类 号：R541[医药卫生—心血管疾病]