JAK/STAT/SOCS3信号通路介导卒中后认知损害的分子机制及中医“活血通络”法对其的干预研究

项目名称： JAK/STAT/SOCS3信号通路介导卒中后认知损害的分子机制及中医“活血通络”法对其的干预研究

项目编号： No.81503370

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 俞璐

作者单位： 上海中医药大学

项目金额： 18万元

中文摘要： 卒中后认知功能障碍与局部脑血流量减少激发的细胞凋亡机制密切相关。前期工作已发现JAK/STAT信号通路是一条参与脑缺血损伤过程的重要途径，在此基础上SOCS3被进一步证实能够负性调节JAK/STAT信号通路。针对JAK/STAT/SOCS3信号通路对脑缺血损伤所致神经元凋亡方面缺乏深入系统的研究，本研究拟进一步探索JAK/STAT表达水平与卒中后神经细胞凋亡、神经功能缺损及卒中后认知功能改变的相关性，及调控SOCS3对JAK/STAT可能产生的影响；同时基于中医认为脑卒中主要病机为“血瘀”，活血化瘀能改善卒中后认知功能障碍，通过采用免疫组化、Western-blot等方法检测相关阳性细胞表达变化，观察HSYA注射液经颈动脉灌注对缺血性脑卒中后脑功能的影响及其改善作用与JAK/STAT/SOCS3信号通路之间可能存在的联系。预计本研究将为缺血性脑卒中及卒中后认知功能障碍的治疗提供有益线索。

中文关键词： JAK/STAT；SOCS3；信号通路；卒中后认知功能障碍；“活血通络”法

英文摘要： Cognitive dysfunction after stroke is closely related to cell apoptosis mechanism motivated by regional cerebral blood flow decrease. Preliminary work has found that JAK/STAT signaling pathway plays a crucial role in cerebral ischemia injury, and SOCS3 is further confirmed that it can negatively regulate JAK/STAT pathway. Aimed at the lack of a thorough system research on JAK/STAT/SOCS3 of neuronal apoptosis caused by cerebral ischemia and reperfusion injury, our research plan to further explore the relationship between expression level of JAK/STAT and apoptosis of nerve cell, neurological impairment and cognitive changes after stroke; possible effect on the expression level of JAK/STAT by regulating SOCS3. Considering blood stasis is the main pathogenesis of stroke, TCM treatment of promoting blood circulation and removing blood stasis can improve the therapeutic effect of stroke, we will observe the possible relationship between the effect on treatment of HYSA injection by external carotid artery perfusion to brain function after ischemic stroke and JAK/STAT/SOCS3 signaling pathway through detecting the expression of Bcl-2, Bax, Caspase-3, P-JAK2, P-STAT3, SOCS3 by the way of immunohistochemical and Western-blot methods. We suppose that the research will provide some useful clues for making treatment on ischemic stroke and cognitive impairment after stroke, and reliable basis for new therapeutic target.

英文关键词： JAK/STAT;SOCS3;signaling pathway;cognitive impairment after stroke;TCM treatment of promoting blood circulation