基于炎性靶标的调节性T细胞过继转输防治蛛网膜下腔出血后脑损伤

项目名称： 基于炎性靶标的调节性T细胞过继转输防治蛛网膜下腔出血后脑损伤

项目编号： No.81471212

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： 孙保亮

作者单位： 泰山医学院

项目金额： 70万元

中文摘要： 炎症反应在蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）及脑损伤中起关键性作用。我们发现调节性T细胞(Tregs)过继转输能显著阻抑脑部炎症反应有关的病理过程。本项目拟首先通过删除Tregs来探明Tregs对SAH后CVS及脑损伤的内源性保护作用，然后对SAH动物预防性及治疗性过继转输自然分离的和经体外扩增的Tregs，对供体Tregs进入受体动物体内的有效性进行示踪分析。定量评价Tregs转输对SAH功能性预后的改善作用；通过对CVS及有关分子通路及调节因子的检测来评价其对CVS的缓解作用；通过对脑水肿、血脑屏障通透性、海马神经元损伤、脑白质损伤等检测来评价其对早期及慢性脑损伤的保护作用；通过检测脑部及系统炎症反应变化，探讨其防治SAH后CVS及脑损伤的抗炎机制。本项目将建立一种全新的、通过抑制炎症反应而缓解SAH后CVS及促进神经功能恢复的Tregs治疗策略。

中文关键词： 蛛网膜下腔出血；脑损伤；炎症反应；细胞治疗；调节性T细胞

英文摘要： Inflammatory responses play key roles in the pathogenesis of cerebral vasospasm and related cerebral injury following subarachnoid hemorrhage (SAH). We have found that regulatory T cells (Tregs) infusion inhibits the pathological process of inflammation-related cerebral disorders and exerts protective effects. In this proposal, mouse Tregs will be deleted to investigate the endogenous protective role of Tregs on cerebral vasospasm and related cerebral injury following SAH. Then, naturally isolated and in vitro expanded and activated Tregs will be infused into mouse and rats both preventively and therapeutically, followed by the induction of SAH. Tregs will be tracked in the recipients after adoptive transfer. The improvement of Tregs on functional outcome of SAH will be evaluated quantificationally, and the inhibitory effects on cerebral vasospasm will be determined, via observing the effects on cerebral artery and related molecular pathway, and also certain regulatory factors. The effects on SAH-related cerebral injury will be investigate via detecting the brain edema, blood-brain barrier, hippocampal neuron damage, and cerebral white matter injury. The anti-inflammatory response mechanism of the protective effects of Tregs on CVS and related cerebral injury after SAH will be verified via observing the immune signaling and the inflammation both in the brain and systemically. The proposed study will develop Tregs as a novel therapeutic strategy based on anti-inflammation to promote the recovery of cerebral vasospasm and related cerebral injury after SAH.

英文关键词： subarachnoid hemorrhage;cerebral injury;inflammatory responses;cell-based therapy;regulatory T cells