心肌梗死后Akt介导的间质细胞源因子1调控循环血内皮祖细胞归巢  

Homing of Circulating Blood Endothelial Progenitor Cells after Myocardial Infarction is Mediated by Akt-SDF-1-signal Pathway

作　　者：赵岚 张少衡[2] 严健 

机构地区：[1]上海市大华医院心内科,上海市200237 [2]上海市杨浦区中心医院心内科,上海市200090

出　　处：《中国动脉硬化杂志》2012年第10期885-889,共5页Chinese Journal of Arteriosclerosis

基　　金：上海市卫生局基金资助(2009015;2010071)

摘　　要：目的探讨急性心肌梗死引起的缺血心肌中Akt-SDF-1信号分子变化情况及其与内皮祖细胞归巢之间的关系。方法利用左前降支冠状动脉结扎术制备大鼠心肌梗死模型后,局部心肌注射Akt抑制剂或等体积二甲基亚砜,分别于术后1、7、14、28天取材,用酶联免疫吸附测定法检测Akt及SDF-1表达变化情况,用流式细胞仪(FACS)及免疫组织化学法检测循环血及局部心肌内皮祖细胞数量变化情况,免疫组织化学法计数血管数量。结果酶联免疫吸附测定结果显示,急性缺血诱导局部心肌Akt和SDF-1表达水平呈进行性升高,FACS及免疫组织化学检测也显示循环血及心肌局部内皮祖细胞数量呈进行性增加,14天达高峰,28天后以上各项指标明显回落,血管计数也显示相同的动态变化,Akt抑制剂显著抑制上述各项指标的动态演变,使其在心肌梗死后各时间点无显著性差异。结论心肌梗死后缺血心肌可通过Akt-SDF-1信号通路调控循环血内皮祖细胞归巢、梗死心脏局部干细胞生存和血管新生。Aim To investigate the expressions of protein kinase B （Akt） and stromal cell-derived factor-1 （SDF-1） and their relations with circulating blood endothelial progenitor cell homing after myocardial infarction （MI）. Methods MI was induced in the Sprague-Dawley （SD） rats by left anterior descending artery ligation. Akt inhibitor or dimethyl sulfoxide （DMSO） was injected into an ischemic zone. At 1,7, 14 and 28 days post-MI, the expression of Akt and SDF-1 in the infarcted hearts were determined by enzyme-linked immunosorbent assay （ELISA）. Circulating blood endothelial progenitor cells （EPCs） or ischemic myocardial EPCs was evaluated by flow cytometry analysis （FACS） or im- munohistochemistry （IH）. The number of vessels was examined by IH. Results ELISA showed that the expression levels of Akt and SDF-1 increased gradually during the early stages of acute ischemia, and reached the highest levels by 14 days post-MI. Similar to the response of Akt and SDF-1 to myocardial ischemia, FACS and IH revealed the same changes of circulating blood EPCs or myocardial EPCs, and blood vessel counting displayed the same dynamic changes. The chan- ges of these observed indices were markedly blocked by Akt inhibitor, which showed no significant difference between all the individual time-points after MI. Conclusion Ischemic myocardiocytes post-MI may regulate homing of circulating blood EPCs, survival of stem cells, and angiogenesis of the infarcted hearts by Akt-SDF-1 signal pathway.

关 键 词：心肌梗死 内皮祖细胞 信号途径 归巢 

分 类 号：R363[医药卫生—病理学]