右美托咪啶对大鼠缺血再灌注损伤心肌的保护作用及机制

项目名称： 右美托咪啶对大鼠缺血再灌注损伤心肌的保护作用及机制

项目编号： No.81471835

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 嵇富海

作者单位： 苏州大学

项目金额： 72万元

中文摘要： 研究表明心肌缺血-再灌注损伤是发生心血管事件的主要原因，而心肌炎症反应是缺血-再灌注损伤的重要原因之一，Toll样受体(TLR)通过活化MyD88、IRAK-1等途径参与了此炎症反应。右美托咪啶是一种高选择性α2肾上腺素能受体激动剂，具有抗炎及器官保护作用。我们前期的研究证实：右美托咪啶可以提高心脏手术患者的生存率及降低心脑血管等不良事件的发生，并通过TLR4受体抑制鼠脑内炎症反应。但右美托咪啶是否能抑制心肌炎症反应及其机制尚不清楚。因此，我们推测右美托咪啶可能通过激活PI3K/Akt激酶，同时通过抑制TLR4受体表达，调控下游信号分子，抑制局部炎症反应和细胞凋亡来减轻心肌缺血再灌注损伤。本课题拟结合离体和在体实验，采用MP-100A-CE 模数转换、基因工程及分子生物学技术等方法，从分子、细胞和整体来探讨右美托咪啶对大鼠缺血再灌注损伤心肌的保护作用及机制，为围手术期心肌保护提供理论依据。

中文关键词： 右美托咪啶；缺血再灌注损伤；麻醉

英文摘要： Studies showed that myocardial ischemia reperfusion injury is the main cause of cardiovascular adverse events. The inflammatory reaction of myocardial is an important factor of ischemia reperfusion injury,and the TLR receptor is involved in the inflammatory response by activation of the MyD88, IRAK-1 pathway. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist, has the effects of anti-inflammatory and organ protection. Our previous studies demonstrated that dexmedetomidine use can improve the survival rate in patients undergoing cardiac surgery and reduce the incidence of cardiovascular adverse events, also can inhibit the inflammatory reaction in rat brain by the pathway of the TLR4 receptor. But if dexmedetomidine could inhibit inflammatory reaction in myocardial and its mechanism is unclear.Therefore, we hypothesized that dexmedetomidine may alleviate the ischemia reperfusion injury by inhibiting the myocardial inflammatory reaction through the ways of activating the PI3K/Akt kinase, and inhibiting the expression of TLR4 receptor, regulation of the downstream signal molecules and reduce the apoptosis. In this study, we will apply MP-100A-CE analog-digital conversion , genetic engineering and molecular biology techniques under the conditions of the in vitro and in vivo experiment from the molecular, cellular and macroscopic levels. The aim of this research is to further exploring the protective effect and mechanism of dexmedetomidine on myocardial ischemia reperfusion injury in rats.The long term goal of this proposal is to provide a theoretical basis for reducing perioperative cardiovascular events.

英文关键词： dexmetomidine;ischemia-reperfusion injury;anesthesia