心肌营养素-1在柯萨奇病毒感染心肌细胞中的作用  

Role of cardiotrophin-1 in cardiomyocytes infected by coxsackievirus

作　　者：朱彬[1] 孙强[1] 刘惊今[1] 贾海波[1] 张烁[1] 

机构地区：[1]哈尔滨医科大学附属第二医院,心血管内科,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2012年第3期227-230,共4页Journal of Harbin Medical University

基　　金：黑龙江省教育厅科学技术研究项目(115811176)

摘　　要：目的探讨在柯萨奇病毒感染心肌细胞中心肌营养素-1(cardiotrophin-1,CT-1)是否通过STAT3途径发挥治疗作用。方法建立柯萨奇B3病毒(CVB3)感染心肌细胞模型,将SD大鼠原代心肌细胞培养48 h后随机分为5组:Con组、Virus组、CT-1组、AG490组、AG490+CT-1组。各组于相应处理后培养30 min,通过Western blot测定STAT3活化水平,分别于培养12 h、24 h、36 h时观察各组心肌细胞病变、搏动情况,测定乳酸脱氢酶(LDH)活性,观察细胞损伤程度。结果 Virus组、AG490+CT-1组、AG490组心肌细胞感染CVB3后,逐步出现细胞病变,细胞搏动停止,培养液中LDH水平明显高于Con组(P<0.05),心肌酶逐渐升高与前一时间点比较(P<0.05)。CT-1组磷酸化STAT3(P-STAT3)水平与Con组相比明显增高(P<0.05),心肌细胞病变明显减轻,LDH释放量显著减少,与Virus组比较差异显著(P<0.05)。AG490+CT-1组较Con组及CT-1组STAT3磷酸化水平显著减低,心肌细胞病变明显,LDH释放量明显增高(P<0.05),与Virus组比较无显著差异(P>0.05)。结论 CT-1在CVB3感染心肌细胞过程中具有心肌保护作用,STAT3磷酸化抑制剂AG490可阻断这一保护作用,提示在病毒感染时CT-1通过介导STAT3磷酸化发挥心肌细胞保护作用。Objective To investigate the role of eardiotrophin-1 in cardiomyocyte infected by coxsackievirus, and then to explore whether the specific role works via STAT3 pathway. Methods Cardiomyocytes.extracted from SD rat were infected by coxsackievirus B3 to establish cellbased viral myocarditis model. Culturing for 48 h, the cardiomyocytes were divided into 5 groups ： Con, Virus, CT-1, AG490 and AG490 ＋ CT-1. After processing for 30 min, the level of phosphorylated STAT3 was detected by Western blot. CVB3-mediated myoeytopathie effects were observed after co-culturing for further 12, 24, 36 h respectively, myocardial cell lesions were examined with LDH assay. Results After CVB3 infection, the beating rate decreased gradually and then stopped. Meanwhile the level of LDH increased significantly in Virus and AG490 groups compared with the Con group （P 〈 0.05）. In Virus and AG490 groups, the level of LDH increased gradually compared with former time points （P 〈 0.05）. In CT-1 group the phosphorylation of STAT3 was prominent compared with Con group （ P 〈 0.05 ）. The degree of cytopathic effect in CT-1 group decreased significantly compared with virus group. Consistently, the release of LDH in CT-1 group was sharply less than virus group （P 〈 0.05 ）. The phosphorylation of STAT3 in AG490 ＋ CT-I group decreased significantly, the cytopathic effect was visible, the level of LDH increased significantly compared with Con and CT-1 group （P 〈 0.05 ）. There was no difference in comparison with Virus group （ P 〉 0.05 ）. Conclusion CT-1 can protect cardiac cells from injury caused by CVB3, and the protective effect can be blocked by AG490, an inhibitor of STA33 phosphorylation, which conclude that the protective role of CT-1 is essentially mediated by STAT3 activation during the infection of CVB3.

关 键 词：病毒性心肌炎 心肌营养素-1 信号转导子和转录激活子3 

分 类 号：R512.5[医药卫生—内科学] R542-21[医药卫生—临床医学]