整合素连接激酶在新生鼠缺氧缺血脑损伤血管修复的信号调控

项目名称： 整合素连接激酶在新生鼠缺氧缺血脑损伤血管修复的信号调控

项目编号： No.81200462

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 张莉

作者单位： 四川大学

项目金额： 23万元

中文摘要： 缺氧缺血脑损伤(HIBD)后，血管再生是脑组织自身修复的重要环节。近年研究发现整合素连接激酶(ILK)可通过蛋白激酶B(PKB)信号通路参与细胞损伤后的修复、迁移以及血管再生等过程。但新生鼠脑缺氧缺血后，ILK是否参与脑血管的修复重建？其可能的机制是什么？ILK/PKB信号通路介导的血管再生与血管内皮细胞生长因子(VEGF)间有无内在联系？新近发现的可介导细胞迁移的PKB底物Girdin蛋白在ILK信号传递中有无关联？起什么作用？二者与VEGF介导的血管再生间的关系均不清楚。本课题将通过建立新生鼠HIBD模型及体外脑血管内皮细胞缺氧缺血模型，观察ILK在血管内皮细胞中的表达，应用ILK、Girdin敲除或高表达方法及PKB信号通路抑制剂，研究ILK/PKB，Girdin及VEGF在介导血管内皮细胞增殖、迁移和血管修复重建中的信号调控机制，为临床治疗HIE提供新思路。

中文关键词： 缺氧缺血性脑损伤；信号转导和转录激活因子3；c-Jun氨基末端激酶；长链非编码RNA；凋亡

英文摘要： Hypoxic-ischemic encephalopathy (HIE) is one of the common and severe neonatal diseases. Angiogenesis has been shown to play an important role in the repairment of brain tissues after hypoxic-ischemic brain injury (HIBD). Recently, integrin-linked kinase (ILK) has been reported to be involved in the regulation of cellular processes including cellular repairment after injury, migration and angiogenesis via protein kinase B (PKB) pathway. However, it is not known whether ILK is involved in cerebral vascular reconstruction and the possible mechanisms in the neonatal rat brain after hypoxia-ischemia. Is there any internal relationship between ILK/PKB signaling pathway mediated-angiogenesis and vascular endothelial growth factor (VEGF)? Is Girdin, a protein mediated-cellular migrarion and PKB substrate, relevant to ILK/PKB signaling transduction? What is the role of Girdin in the signaling pathway? What are the relashionship among ILK/PKB, Girdin and VEGF in angiogenesis after HIBD? All of these scientific questions need to be targeted. In this project, we will establish an HIBD neonatal rats model and an in vitro hypoxic-ischemic model with cultured vascular endothelial cells to investigate the expression of ILK. With these models, we will explore the signaling transduction mechanisms of ILK/PKB, Girdin and VEGF in

英文关键词： Hypoxic-ischemic brain damage；Signal transducer and activator of transcription 3；c-Jun N-terminal kinase；Long non-coding RNA；apotosis