雷帕霉素对柯萨奇病毒B3诱导的大鼠心肌细胞mTOR和eIF-4E表达的调控作用  

Effeet of rapamycin on mTOR and eIF-4E expression in coxsackievirus B3-induced rat myocardial cells

作　　者：陈淳媛[1] 孙跃女[1] 杨作成[1] 蔡姿丽[1] 杨敏[1] 

机构地区：[1]中南大学湘雅三医院儿科,长沙410013

出　　处：《中南大学学报（医学版）》2008年第7期612-617,共6页Journal of Central South University ：Medical Science

基　　金：教育部留学回国启动基金(2006-331);湖南省卫生厅科研基金资助(B2005-072)~~

摘　　要：目的:研究雷帕霉素对柯萨奇病毒B3(coxsackievirus B3,CVB3)诱导的心肌细胞哺乳类雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)和真核起始因子4E(eukaryotic initiation factor-4E,eIF-4E)表达的调控,探讨mTOR/eIF-4E信号传导在病毒性心肌炎(viral myocarditis,VM)的作用。方法:CVB3感染原代培养的SD大鼠心肌细胞建立病毒性心肌炎的细胞模型。根据细胞毒力实验筛选10 nmol/L的雷帕霉素干预CVB3感染的心肌细胞,采用RT-PCR和Western免疫印迹方法检测mTOR和eIF-4E mRNA表达及蛋白质水平。结果:CVB3诱导心肌细胞变性,雷帕霉素可减轻其变性;CVB3使大鼠心肌细胞的mTOR和eIF-4E mRNA和蛋白表达上调,与对照组比较,有统计学差异(P<0.05),雷帕霉素可使CVB3感染的心肌细胞mTOR和eIF-4E mRNA和蛋白表达明显下调,与CVB3组比较,有统计学差异(P<0.05)。结论:雷帕霉素能明显抑制CVB3感染的大鼠心肌细胞mTOR和eIF-4E表达,提示mTOR/eIF-4E信号传导在病毒性心肌炎中可能起重要作用。Objective To observe the effeet of rapamycin, an inhibitor of mammalian target of rapamycin （ mTOR ） , on mTOR and eukaryotic initiation factor-4 E （ eIF-4 E ） expression in coxsackievirus B3 （ CVB3 ） -induced rat myocardial cells and to investigate the role of mTOR/eIF-4E signal pathway in viral myocarditis. Methods To construct a cell model of viral myocarditis with primary cultured myocardial cells. Myocardial cells infected by CVB3 were treated with 10 nmol/L rapamycin according to the cell toxicity test. The mTOR and eIF-4E expressions of cells were determined by RT-PCR and Western Blot. Results Rapamycin inhibited the degeneration of CVB3-induced myocardial cells. Expressions of mTOR and eIF-4E mRNA or protein in CVB3-induced myocardial cells were significantly upregulated compared with the control group （ P 〈 0. 05 ） , and rapamycin （ 10 nmol/L） inhibited the upregnlation （P 〈 0.05 ）. Conclusion Rapamycin can downregnlate the ex-pressions of mTOR and eIF-4E in CVB3-induced myocardial cells, suggesting that mTOR/eIF-4E signal transduction may play an important role in viral myocarditis.

关 键 词：哺乳类雷帕霉素靶蛋白 真核起始因子4E 柯萨奇病毒B3 心肌细胞 

分 类 号：R542.21[医药卫生—心血管疾病]