干预NF-κB活化对脑出血后不同时期炎症反应和细胞凋亡的影响

项目名称： 干预NF-κB活化对脑出血后不同时期炎症反应和细胞凋亡的影响

项目编号： No.81501054

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： 张泽立

作者单位： 山东大学

项目金额： 19万元

中文摘要： 脑出血（ICH）后的原发性损害常无法避免，而继发性损害在ICH后一段时间内发生，可对其干预来改善预后。申请人研究结果和相关文献表明，血肿周围脑组织中NF-κB活化与细胞死亡和预后关系密切，但NF-κB活化促进细胞凋亡，还是其在细胞凋亡后表达增高以保护神经细胞目前尚无定论。结合国内外相关研究，我们设想NF-κB在ICH后存在早期促进炎症反应及细胞凋亡和晚期减轻炎症反应和细胞凋亡的双向作用。为验证该设想，我们拟制作脑出血体内和体外模型，在ICH后的不同时期，分别应用NF-κB激活和抑制药物、基因过表达、RNAi技术来干预NF-κB活化，检测NF-κB活化及各亚基表达、相关炎性因子表达、细胞凋亡及相关因子表达，探究NF-κB在ICH后不同时期对炎症反应、细胞凋亡的具体作用机制，为今后在ICH后不同时期针对NF-κB采取不同的干预策略，进而减轻炎症反应，减少细胞凋亡，改善患者预后提供新的理论依据。

中文关键词： 脑出血；NF-κB活化；炎症反应；细胞凋亡；干预

英文摘要： Unlike the primary damage after intracerebral hemorrhage (ICH), which is inevitable in most cases, the secondary damage happens in a period of time after ICH and interference measures can be taken on to improve the prognosis. According to the results of our previous research and related reference, apoptosis and prognosis are closely related to the NF-κB activation. It is still questionable, however, whether NF-κB activation directly leads to poor functional outcome or it is just a compensatory mechanism to protect the brain tissue from damage. Based on the overseas and domestic research, we propose that NF-κB has a dual role that promotes inflammatory response in the early stage and is neuroprotective in the late stage after ICH. To verify the above assumptions, we plan to produce ICH model in vivo and vitro, interfere NF-κB activation with drugs, overexpression and RNAi technology, detect the NF-κB activation, related inflammatory factors, apoptosis and related factors, and explore the effects of NF-κB activation on inflammatory response, apoptosis at different stages after ICH. We hope, based on the results of these researches, different intervention strategies can be applied at different stages after ICH to relieve the inflammatory response, reduce the apoptotic cells and then improve the prognosis.

英文关键词： intracerebral hemorrhage;NF-κB activation ;inflammatory response ;apoptosis;interventions