AKT/PI3K信号通路介导的干细胞动员在抗心梗后心律失常中的作用  

Study on the role of stem cell mobilization mediated by AKT/PI3K signaling pathway in the cardiac arrhythmia after myocardial infarction

作　　者：苏枫[1] 王加红[1] 陈楠楠[1] 姚建华[1] 唐静辉[1] 龚群林[1] 张少衡[1] 

机构地区：[1]同济大学附属杨浦医院心内科,上海市200090

出　　处：《中国心血管病研究》2014年第8期732-735,共4页Chinese Journal of Cardiovascular Research

基　　金：上海市卫生局课题面上项目（项目编号：21034334）

摘　　要：目的 探讨心肌梗死（MI）后丝氨酸/苏氨酸/磷脂酰肌醇-3激酶（AKT/PI3K）信号通路介导的心脏干细胞（CSCs）动员对抗心梗后心律失常的影响.方法 将大鼠随机分为5组,每组20只：对照组（CON组）、结扎组（LI组）、结扎＋注射组（LI＋LY组）、缺血预处理＋结扎组（IP＋LI组）、缺血预处理＋结扎＋注射组（IP＋LI＋LY组）.采用结扎LAD的方法建立心梗模型,采用流式细胞分析、ELISA法等检测各组AKT/PI3K信号通路相关指标的表达情况及心律失常的发生情况.结果 LI＋LY组炎症反应显著高于其他各组,IP＋LI组显著低于IP＋LI＋LY组、LI＋LY组、LI组（P＜0.05）;IP＋LI组比LI组CD34＋、Oct4＋细胞的数量多（P＜0.05）;与CON组相比,IP＋LI组SDF-1表达显著增加,LI＋LY组及LI组表达明显减少（P＜0.05）;与LI组比较,IP＋LI组心律失常的发生率明显降低,QTc间期也明显缩短（P＜0.05）.结论 通过激活内源性Akt/PI3K信号通路,可有效促进内源性心脏干细胞动员及归巢,使心肌细胞再生,从而改善心脏功能,降低心肌缺血后室性心律失常的发生.Objective To explore the influence of CSCs stem cell mobilization mediated by AKT/PI3K signaling pathway on the eardiae arrhythmia after myocardial infarction. Methods 100 Male rats were divided randomly into five groups （n=20） including control group （CON）, ligation group （LI）, ligation＋LY294002 group （LI＋LY）, isehemie preeonditioning＋ligation （IP＋LI）, isehemie preeonditioning＋ligation＋LY294002 （IP＋LI＋LY）. MI model was induced by left anterior descending artery ligatior （LAD）, flow cytometry and ELISA were used to detect the expression of AKT/PI3K related indicators, and the incidence of cardiac arrhythmia was recorded. Results LI＋LY group had a significantly higher inflammatory reaction than CON group and other groups, and IP＋ LI group was significantly lower than IP＋LI＋LY, LI＋LY, LI group （P〈0.05）. The number of CD34＋, Oct4＋ in IP＋LI group were significantly more than LI group（P〈0.05 ）. Compared with CON group, the expression of SDF-1 in IP＋LI group were significantly increased, but they were decreased signifieantly in LI＋LY group and LI group （P〈0.05）. Compared with LI group, the incidence of arrhythmia in IP＋LI group was obviously lower, QTe interphase also significantly reduced（P〈0.05）. Conclusion By activating endogenous PI3K/Akt signaling pathway, which earl effectively promote endogenous cardiac stem eeUs mobilization and homing, enhaneemant of myocardial cell regeneration, and imorove heart funetion, reduce the occurrence of arrhvthmia after MI.

关 键 词：信号通路 心肌梗死 心律失常 干细胞动员 丝氨酸苏氨酸激酶 1-磷脂酰肌醇-3激酶 

分 类 号：Q95-33[生物学—动物学] R541.7[医药卫生—心血管疾病]