右美托咪定心脏保护效应的miRNA机制研究

右美托咪定为高选择性 α2受体激动剂，具有镇静、镇痛、抗焦虑、抑制交感神经兴奋等作用，现作为麻醉辅助药用于手术和 ICU 镇静。近期研究发现右美托咪定具有心脏保护作用，如抗缺血再灌注损伤、抗心律失常，从而总体上降低术后心脏相关并发症的发生。其抗缺血再灌注损伤作用机制一方面可能与抑制中枢的交感活性，降低心率、增加氧供、降低氧耗相关，另一方面可通过缺血预处理机制，激活相关促存活信号通路抗缺血再灌注损伤。同时，使用该药后儿茶酚胺释放减少，迷走神经相对兴奋，可降低手术及麻醉操作引起的应激反应，并可与咪唑啉受体结合，使其具有抗心律失常作用。总体而言，其保护作用的确切机制尚不明确，miRNAs 调节右美托咪定心脏保护的分子机制还不清楚。我们将从整体、器官、组织、细胞、分子水平深入研究miRNA调控右美托咪定心脏保护的分子机制。

Dexmedetomidine is a highly selective α2 adrenoreceptor agonist, which exhibits a wide range of effects, including sedation, analgesia, antianxiety, sympatholytic properties. As an anaesthetic adjuvant, it is widely used in operative processes and ICU sedation. Recently it has been demonstrated that it has cardioprotective effects, such as anti-ischemia/reperfusion injury, anti-arrhythmic and prevention of postoperative cardiac complications. On one hand, the mechanisms of anti-ischemia/reperfusion injury may be related to attenuating sympathetic activation, dropping heart rate, increasing oxygen supply while decresing the consumption, so that it can keep the myocardial oxygen balance; on the other hand, dexmedetomidine preconditioning is mediated by the activation of pro-survival signal pathway after cardiac α2 receptor stimulation. In addition, it can attenuate catecholamine release, make vagus nerve stimulation relatively, reduce the stress response caused by operation and anesthesia, which result in its anti-arrhythmic effect. Also, because of its pharmacological structure, imidazoline receptors play an important role in anti-arrhythmic. In general, the exact mechanisms of its cardioprotective effects are still unclear. Future researches need to aim at investigating the molecular and genetic mechanisms of its cardioprotective effects . We will investigate the molecular and genetic mechanisms of its cardioprotective effects at the system, organ, tissue, cellular and molecular levels.