项目名称: RIP1/RIP3通路调控脑出血后细胞程序性坏死的机制研究
项目编号: No.81501012
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: 苏兴奋
作者单位: 福建医科大学
项目金额: 17.5万元
中文摘要: 脑出血(Intracerebral hemorroage, ICH)后的细胞坏死调控机制目前尚未完全清楚。新近的研究发现一些细胞坏死可通过受体相互作用蛋白激酶1(RIP1)和RIP3两个关键蛋白激酶调控,并可被小分子抑制剂Necrostatin-1(Nec-1)抑制,这种细胞坏死被称作程序性坏死或Necroptosis。但目前尚不明确该机制是否也在脑出血细胞坏死中发挥作用。本课题拟通过体内、体外研究,运用抑制剂及基因干扰技术,深入探讨RIP1/RIP3通路在调控小鼠脑出血后细胞坏死中的作用机制,并剖析Nec-1在小鼠ICH中的神经保护作用机制。通过本课题的研究,以期阐明ICH后细胞程序性坏死调控的分子机制,为后续研究提供基础和实验依据,有望为脑出血研究和治疗提供新的靶点和方向。
中文关键词: 脑出血;程序性坏死;受体相互作用蛋白激酶1;受体相互作用蛋白激酶3;Necrostatin-1
英文摘要: The mechanism of necrotic cell death after intracerebral hemorroage (ICH) is not full understood yet. Recent studies found that some kind of necrotic cell death, named programmed necrosis or necroptosis, is regulated by receptor interacting protein kinase 1 (RIP1) and RIP3, and can be inhibited by a small molecular weight chemical necrostatin-1 (Nec-1). However, it’s still unknown whether RIP1/RIP3 pathway has their role in necrosis after ICH. The present study will investigate the role of RIP1/RIP3 pathway on the necrotic cell death after ICH through using specific inhibitor or gene inhibition technique in in vivo and in vitro ICH models. And we will further explore the possible neuroprotective mechanisms of Nec-1 in mice after ICH. Through this study, we hope to further clarify the molecular mechanism of necroptosis in ICH, which will provide foundation and data for future studies and may lead to new targets and directions for therapy and study in ICH.
英文关键词: ICH;Necroptosis;RIP1;RIP3;Necrostatin-1