BMSC-MVs通过影响自噬以调控NLRP3介导的细胞焦亡改善脑缺血再灌注损伤的功能障碍及机制研究

脑缺血再灌注损伤（I/R）可造成严重的神经功能障碍，其治疗是临床一大难题。文献报道NLRP3炎症小体介导的细胞焦亡是脑I/R损伤的重要组成部分，而自噬的激活可以抑制组织I/R损伤中的炎症反应。我们在前期研究发现，骨髓间充质干细胞（BMSCs）移植能通过调控自噬促进脑缺血大鼠神经功能恢复，且BMSCs分泌的细胞微囊泡（BMSC-MVs)可激活PI3K-AKT通路以减少细胞凋亡。最新文献指出MVs的正向保护作用机制与自噬的激活和炎症的缓解有关，但在脑I/R损伤的研究中尚未有报道。由此我们假设：在脑I/R损伤中，BMSC-MVs可通过调控自噬逆转NLRP3炎症小体介导的细胞焦亡，改善其神经功能障碍。本研究拟通过体内和体外实验，利用基因沉默和超表达等技术，探明BMSC-MVs在脑I/R中的作用，验证BMSC-MVs是否影响自噬以调控NLRP3，从而为缺血性脑卒中的治疗提供新思路和实验基础。

Cerebral ischemia reperfusion (I/R) injury can lead to severe dysfunction,and its treatment is difficult. It is reported that NLRP3 inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury. The activation of autophagy can inhibit the inflammatory reaction in I/R injury. We found in previous studies that bone marrow mesenchymal stem cells (BMSCs) transplantation is an effective means of promoting the nerve function recovery of cerebral ischemia rats by regulating the autophagy, and cells-microvesicles (BMSC-MVs) secreted by BMSCs can activate the PI3K-AKT pathway to reduce cell apoptosis. The latest reports indicates that the positive protective mechanism of MVs is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in the study of cerebral I/R injury. Therefore, we hypothesize that BMSC-MVs can reverse neurofunction of NLRP3 inflammasome-mediated cell pyroptosis via autophagy in cerebral I/R injury. We will simulate the cerebral I/R injury model in vivo and vitro, to explore the mechanism of BMSC-MVs in cerebral I/R injury and investigate if BMSC-MVs regulate NLRP3 by affecting autophagy by using siRNA gene overexpression and other technologies,which provides a new thinking and experimental basis for treating patients with ischemic stroke.