EdCC通过MEK-ERK信号通路减轻小鼠心肌缺血再灌注损伤  

EdCC reduces myocardial ischemia-reperfusion injury via MEK-ERK signaling pathway

作　　者：蒋智[1] 贾中申 吴玥婷[1] 韦方[1,2] 

机构地区：[1]贵州省人民医院心内科,贵州省心血管病研究所,贵州贵阳550002 [2]贵州医科大学,贵州贵阳550004

出　　处：《中国病理生理杂志》2016年第2期221-227,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金地区科学基金资助项目(No.81460050);贵州省科技厅科学技术基金(黔科合J字[2014]2112号);贵州省卫生厅科学技术基金资助项目(No.gzwkj2013-1-006)

摘　　要：目的:研究子宫内膜干细胞(endometrial stem cells,EnSCs)来源细胞因子"鸡尾酒"(EnSC-derived cytokine cocktail,EdCC)对心肌缺血再灌注损伤的影响及MEK-ERK信号通路的作用。方法:建立小鼠心肌缺血再灌注损伤模型,用TTC/Evans blue染色评估心梗面积,TUNEL染色检测细胞凋亡,Western blot检测ERK1/2磷酸化水平和cleaved caspase-3表达。结果:EnSCs具有间充质干细胞特性,表达CD90,不表达CD34和CD45。EdCC的表皮生长因子(EGF)含量为(6 811±312)ng/g蛋白。经尾静脉注射EdCC可显著升高心肌ERK1/2磷酸化水平,明显降低梗死面积,减少梗死周边区凋亡细胞数目,抑制capase-3活化。MEK1特异性阻断剂PD98059(5 mg/kg)抑制EdCC介导的ERK1/2磷酸化,并抵消上述心肌保护效应。EGF受体特异性阻断剂AG-1487(6 mg/kg)只能部分抵消EdCC的心肌保护作用,而单纯注射EGF不能缩小梗死面积。结论:EdCC通过激活MEK1-ERK1/2信号通路减轻心肌缺血再灌注损伤,EGF受体是该通路重要组成部分。该结果对目前成体干细胞移植治疗模式——从细胞转移到细胞因子,具有重要的理论意义。AIM ： To investigate the myocardial protective effect of endometrial stem cell （EnSC） -derived cyto- kine cocktail （EdCC） on myocardial ischemic reperfusion injury and the MEK-ERK signaling pathway. METHODS： A mouse model of myocardial ischemic reperfusion injury was established. Infarct area, cell apoptosis, and expression of cleaved caspase-3 and phosphorylatied ERK1/2 were determined by TTC/Evans blue staining, TUNEL assay and Western blot, respectively. RESULTS： The mesenchymal characteristics were observed in the EnSCs with expressing CD90 and in absence of CD34 and CD45. EdCC contained （6 811 ± 312） ng/g epidermal growth factor （EGF） protein. The phospho- rylation of ERK1/2 markedly increased after injection of EdCC, but was abolished by MEK1 inhibitor PD98059 （5 mg,/ kg）. EdCC decreased the infarct area and apoptotic cell number in the border zone and inhibited caspase-3 activation. However, the effects were abolished by MEK1 specific inhibitor PD98059. EGF did not decrease the infarct area, but the EGF receptor antagonist AG-1487 （6 mg/kg） partly abolished the myocardial protective effect of EdCC. CONCLUSION： EdCC protects the myocardium from ischemic reperfusion injury via activating MEK1-ERK signaling pathway, indicating an essential role in the transmission of stem cell therapy from the cell transplantation to cytokine based strategy.

关 键 词：子宫内膜干细胞来源细胞因子“鸡尾酒” MEK-ERK信号通路 心肌梗死 缺血再灌注损伤 

分 类 号：R363[医药卫生—病理学] R542.22[医药卫生—基础医学]