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论著:PI3K信号途径调节心肌梗死大鼠心脏干细胞动员
Mobilization of Cardiac Stem Cells in Rat Hearts with Myocardial Infarction Mediated By PI3K/AKT Signal Pathway
赵岚 张焱 严健
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作者单位:上海市大华医院心内科
中文关键字:心肌梗死;心脏干细胞;信号通路;动员
英文关键字:Myocardial infarction; Cardiac stem cells; Signal pathway; Mobilization
中文摘要:目的:探讨心肌梗死后PI3K信号通路对大鼠心脏干细胞(CSCs)动员及其修复损伤心肌的影响。方法:用冠状动脉左前降支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周,2周,4周和8周取材,利用酶联免疫吸附试验(ELISA)检测Akt表达变化情况,利用免疫组化(IH)检测局部心肌CSCs数量变化情况,通过TTC染色检测梗死面积。结果:ELISA结果显示,急性缺血诱导局部心肌Akt表达水平呈进行性升高, IH检测显示心肌局部CSCs 数量呈进行增加,2周达高峰,4周后以上各项指标明显回落,心肌梗死面积则逐渐扩展,8周时明显大于其他时间点,Akt抑制剂显著抑制上述各项指标的动态演变,使心肌梗死面积进一步恶化。结论:心肌梗死后缺血心肌可通过Akt信号通路调控梗死心肌局部CSCs动员及其修复梗死心肌。
英文摘要:Objective: To investigate the expressions of PI3K/AKT signals and their relations with mobilization and functions of local myocardial cardiac stem cells (CSCs) after myocardial infarction. Methods: Myocardial infarction (MI) was induced in the SD rats by left anterior descending artery ligation. Akt inhibitor or DMSO was injected into an ischemic zone. At 1, 2, 4 and 8 weeks post-MI, the expression of phospho Akt in the infarcted hearts were determined by enzyme-linked immunosorbent assay (ELISA). Ischemic myocardial CSCs was evaluated by immunohistochemistry (IH). Infarct area was examined by TTC staining. Results: ELISA showed that the expression levels of phospho Akt increased gradually during the early stages of acute ischemia, and reached the highest level by 2 weeks post-MI. Similar to the response of phospho Akt to myocardial ischemia, IH reavels the same changes of myocardial CSCs, and infarct area displayed the gradual expansion and showed more significantly at 8 weeks post-MI than at other time points. The changes of these observed indices were markedly blocked by Akt inhibitor, which showed no significant difference between all the individual time-points after MI. The infarct area was further deteriorated by using Akt inhibitor. Conclusions: Ischemic myocardiocytes post-MI may regulate mobilization and function of local endogenous CSCs by PI3K/AKT signal pathway.
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