miR-146a介导bcl-2/beclin-1信号通路调节自噬在右美托咪定抗肠缺血再灌注损伤中的作用及机制

肠缺血再灌注（I/R）损伤可致多器官功能障碍，围术期死亡率极高。研究证明自噬是肠I/R肠粘膜细胞损伤的重要机制之一，低氧诱导的miR-146a可以通过下调bcl-2的表达，进而促进软骨细胞的自噬；我们前期研究证明，自噬调节通路bcl-2/beclin-1在肾I/R损伤中发挥重要作用，但在肠I/R肠损伤中作用不清。右美托咪定作为一种新型的α2肾上腺素能受体激动剂，可以提高肠组织中bcl-2的表达减轻肠I/R损伤。因此，我们推测，右美托咪定可能通过miR-146a调控bcl-2/beclin-1信号通路，从而调节肠I/R肠粘膜自噬水平发挥肠保护作用。本研究拟建立miR-146a转基因小鼠的肠I/R在体模型及肠粘膜上皮细胞缺氧复氧的离体模型，深入探究右美托咪定抗肠I/R损伤的作用及机制，为临床防治肠I/R损伤提供新策略。

Intestinal ischemia reperfusion (I/R) injury can cause multiple organ dysfunction, and perioperative mortality is extremely high.Studies have proved that autophagy is one of the important mechanisms of intestinal I/R mucosal cell injury. Hypoxic-induced mir-146a can promote the autophagy of chondrocytes by down-regulating the expression of bcl-2.Our previous studies have proved that the autophagy regulatory pathway bcl-2/beclin-1 plays an important role in renal I/R injury, but its role in intestinal I/R injury is unclear.Dexmedetomidine, as a novel alpha 2 adrenergic receptor agonist, can improve the expression of bcl-2 in intestinal tissues and alleviate intestinal I/R injury.Therefore, we speculated that dexmedetomidine may regulate bcl-2/beclin-1 signaling pathway through mir-146a, thereby regulating intestinal I/R intestinal mucosal autophagy to play a protective role.The purpose of this study was to establish an in vivo model of intestinal I/R in mir-146a transgenic mice and an in vitro model of intestinal epithelial cells hypoxia and reoxygenation, so as to further explore the effect and mechanism of dexmedetomidine on intestinal I/R injury and provide a new strategy for clinical prevention and treatment of intestinal I/R injury.