端粒酶逆转录酶调控新生鼠缺氧缺血脑损伤神经修复的新机制

项目名称： 端粒酶逆转录酶调控新生鼠缺氧缺血脑损伤神经修复的新机制

项目编号： No.81501302

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： 李姣

作者单位： 四川大学

项目金额： 18万元

中文摘要： 血管再生和神经再生是脑损伤后神经修复的重要环节。近年来的研究发现端粒酶逆转录酶（TERT）能够调节血管再生和神经再生过程。在前期研究中，我们发现TERT在脑缺氧缺血后表达增加，并能通过减少细胞凋亡发挥神经保护作用。但是，新生动物在缺氧缺血脑损伤（HIBD）后，TERT与血管再生和神经再生的关系是什么？TERT是否参与了HIBD后血管再生和神经再生的调控？其调控的机制是什么？目前尚不清楚。本课题将通过建立新生鼠HIBD模型及体外脑血管内皮细胞和神经干细胞缺氧缺血模型，研究TERT的表达及其与血管再生和神经再生的关系。通过应用基因转染技术抑制或增加TERT的表达，探讨TERT对损伤后血管再生和神经再生的调控及对神经功能恢复的影响。并进一步阐明TERT对血管再生和神经再生调控的相关机制。对TERT的深入研究可望揭示其在脑损伤后神经保护作用的新途径、新机制，为临床治疗新生儿缺氧缺血脑病提供新思路。

中文关键词： 端粒酶逆转录酶；神经再生；血管再生；缺氧缺血；脑损伤

英文摘要： Angiogenesis and neurogenesis play significant role in nerve repair after brain damage. Recent researches have demonstrated that TERT was involved in the regulation of angiogenesis and neurogenesis. In previous study, we have found that TERT was induced after hypoxic-ischemic brain damage (HIBD) and played a neuroprotective role by decreasing neuronal apoptosis. However, what’s the relationship between TERT and angiogenesis, neurogenesis after HIBD? Whether TERT is involved in the regulation of angiogenesis and neurogenesis after HIBD? And what’s the regulating mechanism? Are still unclear. In this project, we will establish an HIBD neonatal rat model and an in vitro hypoxic-ischemic model with cultured vascular endothelial cells and neural stem cells to investigate the expression of TERT and its relationship with angiogenesis and neurogenesis. With these models, we will explore the regulating role of TERT in angiogenesis and neurogenesis by using the technology of gene transfection to inhibit or increase the expression of TERT. And we will further explore the regulating mechanisms of TERT in angiogenesis and neurogenesis. We believe that our studies will explore a new neuroprotective pathway and mechanism of TERT in brain damage, and provide new insights in the therapeutic strategies of neonatal hypoxic ischemic encephalopathy.

英文关键词： telomerase reverse transcriptase;neurogenesis;angiogenesis;hypoxia-ischemia;brain damage