心肌miRNA-1和miRNA-21在七氟醚后处理老龄大鼠心肌效果中的差异性表达及意义

Differential Expression and Potential Role of Myocardial miRNA-1 and miRNA-21 in Aging Reperfused Hearts treated by Sevoflurane Postconditioning

目的初步探索心肌miRNA-1和miRNA-21在七氟醚后处理(Sevo Po C)老龄心肌缺血/再灌注损伤(I/RI)效果中的表达及其潜在作用。方法建立年轻(3~4月龄)和老龄(22~24月龄)大鼠在体心梗模型(30 min冠脉结扎,恢复血流120 min),给予Sevo Po C(1.0 MAC),采用TTC法检测心梗面积、TUNEL法检测心肌细胞凋亡和Taq Man探针法检测心肌miRNA-1和miRNA-21表达水平,并分别行miRNA-1和miRNA-21与细胞凋亡的相关性分析。结果 Sevo Po C可明显降低年轻大鼠心肌I/RI引起的心肌梗死面积增加、凋亡水平升高(所有P<0.05),但此效果在老龄大鼠中消失(所有P>0.05)。大鼠心肌I/RI可导致心肌miRNA-1和miRNA-21升高,但老龄较年轻组增幅更为明显(P<0.05);Sevo Po C能使年轻大鼠心肌miRNA-1和miRNA-21降至基础水平(P<0.05),但老龄大鼠经Sevo Po C后这两种水平仍较高(P<0.05)。相关分析结果显示,miRNA-1和miRNA-21均与凋亡水平呈现较强的正相关(P<0.05)。结论Sevo Po C并不能对在体老龄大鼠心肌I/RI发挥保护作用,表现为心肌梗死面积和细胞凋亡水平不下降,其机制可能与缺血后老龄心肌miRNA-1和miRNA-21过度激活有关。

Objective To investigate the expression and potential role of the myocaridal mi RNA-1 and mi RNA-21 in sevoflurane postconditioning treated aging rat heart after ischemia/reperfusion injury（I/RI）. Methods Young（3-4 months） and old（22-24 months） rats were subjected to 30 mins coronary artery ligation, followed by 120 mins of reperfusion, with or without sevoflurane postconditioning（1.0 MAC）. The infarct size（TTC method）, myocardial apopotsis level（TUNEL method）, and the myocardial expression of mi RNA-1 and mi RNA-21（Taq Man Probe method） were detected. In addition, a correlation analysis between mi RNAs and apoptosisi level was also performed. Results Sevo Po C significantly reduced the myocardial infarct size and apoptosis level after I/RI in young rats（both P〈0.05） but not in old rats（both P〉0.05）. The increases in myocardial mi RNA-1 and mi RNA-21 levels elicited by I/RI were both more obvious in old rats than those in young rats（both P〈0.05）. Sevo Po C decreased the levels of myocardial mi RNA-1 and mi RNA-21 to the baseline in young rats（P〈0.05）, but not in old rats（P〈0.05）. Moreover, the apoptosis levels were significantly positively correlated with the expression of mi RNA-1 and mi RNA-21（both P〈0.05）. CondusionSevo Po C could not confer cardioprotection in old rat hearts subjected to I/RI in terms of irreduction in infarct size and apoptosis levels, partly due to the postischemia over activation of mi RNA-1 and mi RNA-21 in old rat hearts.