TLR4/MYD88/NF-κB信号通路在虾青素对蛛网膜下腔出血后脑损伤保护作用的机制研究

项目名称： TLR4/MYD88/NF-κB信号通路在虾青素对蛛网膜下腔出血后脑损伤保护作用的机制研究

项目编号： No.81501022

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： 张翔圣

作者单位： 中国人民解放军东部战区总医院

项目金额： 17.5万元

中文摘要： 蛛网膜下腔出血后脑损伤是SAH不良预后的重要原因，但目前仍无有效治疗方案。国内外研究发现，SAH后氧化损伤与炎症反应在脑损伤发生发展过程中起关键作用。虾青素是自然界最强的抗氧化剂，国内外大量研究围绕其强抗氧化机制展开。而前期我们同样证实虾青素能够显著减轻SAH后脑组织氧化应激损伤，但是鲜有研究关注其其他保护作用。申请人在前期研究基础上发现虾青素同样能够减轻SAH后炎症损伤，并且抑制NF-ĸB相关通路，与国内外相关研究报道吻合。因此，本课题将围绕TLR4/MYD88/NF-ĸB信号通路是否在虾青素对抗SAH后炎症反应起重要作用进行展开，拟通过体内、体外两个范畴，在上下游分别应用RNA干扰及过表达技术，结合分子生物学及组织形态学研究进行验证。通过本课题可为虾青素中枢神经保护作用提供新的机制，为后续虾青素临床转化研究提供新的治疗策略。

中文关键词： 蛛网膜下腔出血；脑损伤；虾青素；Toll样受体4；神经保护

英文摘要： Brain injury is the primary cause of poor prognosis in subarachnoid hemorrhage (SAH). And there is no effective treatment. Based on the latest research in the world, oxidative damage and inflammatory response played important roles in the development of brain injury after SAH. Astaxanthin (ATX) is the most potent antioxidant in the nature world. And mounting studies mainly centered on the mechanism of anti-oxidative. In our previous study, we also proved that ATX could ameliorate oxidative stress in the SAH. However, few studies concentrated its other functions. We previously found that ATX could also reduce inflammation response in the SAH, and inhibit NF-ĸB related pathway. These findings are consistent with previous studies. Hence, we will use RNAi in both vivo and vitro with the methods of molecular biology and histology combined to analyze the potential role of TLR4/MYD88/ NF-ĸB in the anti-inflammation of ATX in SAH. The current study will establish a new rationale for the neuro-protective effects of ATX, and provide a novel therapeutic strategy for clinical translational research of ATX.

英文关键词： subarachnoid hemorrhage;brain jury;astaxanthin;Toll-like receptor 4;neuroprotective