TREM2促进心肌梗死后心肌细胞再生的机制研究

Mechanism of TREM2 in promoting cardiomyocyte regeneration after myocardial infarction

目的:探究髓系细胞触发受体2(TREM2)促进心肌梗死(MI)后心肌细胞再生的机制。方法:收集健康对照者和MI患者血浆样本,检测血浆TREM2浓度。构建C57BL/6和TREM2基因敲除(TREM2-/-)小鼠左前降支结扎MI模型。免疫蛋白印迹(Western blot)和荧光定量PCR检测梗死区和梗死边缘区TREM2和细胞周期素A2(CyclinA2)蛋白和mRNA表达水平,HE染色和Masson染色评估心肌损伤程度和梗死面积。结果:MI患者血浆TREM2的表达较健康对照者升高(P<0.05)。野生型小鼠MI后心脏中TREM2和CyclinA2 mRNA表达水平增加(P<0.05),TREM2在MI后1、2、3 d逐渐增加(P<0.05),而CyclinA2在MI后第2天心脏表达达到高峰(P<0.05)。TREM2基因敲除后梗死区和梗死边缘区CyclinA2的蛋白表达水平减少(P<0.05)。HE染色和Masson染色显示TREM2-/-小鼠心肌损伤程度较野生型小鼠加重,梗死面积增加(P<0.05)。结论:MI患者血浆TREM2表达水平增加。MI后TREM2可能会通过CyclinA2促进心肌再生,减轻心肌损伤,减小梗死面积。

Objective:To explore the mechanism of triggering receptor expressed on myeloid cells 2(TREM2)in promoting cardiomyocyte regeneration after myocardial infarction.Methods:Plasma samples were initially obtained from healthy controls and patients with myocardial infarction to measure plasma TREM2 concentration.Myocardial infarction(MI)was induced by ligating the left anterior descending branch in C57BL/6 and TREM2 gene knockout(TREM2-/-)mice.Western blot and fluorescence quantitative PCR were respectively used to detect the expression of cyclinA2 protein and mRNA expression of TREM2 and CyclinA2 in infarct area and infarct border zone.HE and Masson staining were used to evaluate myocardial injury and infarct area.Results:Plasma TREM2 level in MI patients was significantly higher than that in healthy controls(P<0.05).mRNA expression of TREM2 and CyclinA2 was increased in the heart of wild-type mice after myocardial infarction.TREM2 expression gradually was increased on the 1 st,2 nd and 3 rd day after myocardial infarction(P<0.05)and CyclinA2 expression reached its peak on the 2 nd day(P<0.05).After TREM2 gene knockout,cyclinA2 protein expression was significantly down-regulated in the infarct area and infarct border zone(P<0.05).HE and Masson staining showed that myocardial injury in TREM2-/-mice was more serious,with significantly expanded infract area compared to the wild-type mice(both P<0.05).Conclusion:Plasma TREM2 level in MI patients significantly increases.After myocardial infarction,TREM2 may promote myocardial regeneration and reduce myocardial injury and infarct area via cyclinA2.