右美托咪定通过lncRNA-BCAR4吸附miR-665调控CB2减轻心肌缺血/再灌注损伤的机制研究

LncRNA和microRNAs互作调节可作为一种新型的心脏保护策略。右美托咪定具有心脏保护作用，但保护作用是否通过调节lncRNA和microRNAs产生效应还没有报道。我们前期研究表明，右美托咪定可减轻缺血/再灌注损伤，上调表达lncRNA-BCAR4,下调表达miRNA-665，结合生物信息学分析，我们提出假说：右美托咪定可能通过上调表达lncRNA-BCAR4抑制miRNA-665表达，上调表达CB2，激活PI3K/AKT信号通路产生心脏保护效应。为了验证这一假说，我们将通过细胞实验明确右美托咪定上调表达lncRNA-BCAR4，抑制miRNA-665表达，上调表达CB2；用大鼠在体心脏缺血/再灌注模型进一步证明；结合分子生物学实验，阐明右美托咪定通过lncRNA-BCAR4/microRNA-665/CB2/PI3K/AKT轴产生心脏保护效应，为围手术期心脏保护提供新靶点。

The interaction of lncRNAs with microRNAs serves as a novel cardioprotective strategy. Dexmedetomidine has been demonstrated that it has cardioprotective effects, while no studies are focused on the involvement of the regulation of interaction of lncRNAs with microRNAs in its cardioprotective effects. Our preliminary findings demonstrate that dexmedetomidine can protect the hearts against ischemia/reperfusion injury, upregulate expression of lncRNA-BCAR4, decrease expression of microRNA-665 and activate PI3K/AKT signaling pathway. Based on bioinformatics analysis, we hypothesize, therefore, that dexmedetomidine exerts cardioprotective effect via the upregulation of lncRNA-BCAR4, inhibition of microRNA-665, up-regulation of CB2， and activation of PI3K/AKT pathway. To validate the hypothesis, we will study that dexmedetomidine upregulates expression of lncRNA-BCAR4, inhibiting expression of microRNA-665, affecting the expression of CB2， and activating PI3K/AKT pathway in vitro and further confirm them in vivo. This study will also explore the molecular mechanisms and pathways underlying cardioprotection of dexmedetomidine via microRNA-665 and provide the novel targets for perioperative cardioprotection.