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Tβ4稳定HIF-1α功能的信号通路及其促进大鼠心梗后血管新生的作用机制研究

Tβ4稳定HIF-1α功能的信号通路及其促进大鼠心梗后血管新生的作用机制研究
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  • 批准号:91539111
  • 批准年度: 2015年
  • 学科分类:冠状动脉性心脏病(H0206) |
  • 项目负责人:杨进福
  • 负责人职称:主任医师
  • 依托单位:中南大学
  • 资助金额:80万元
  • 项目类别:重大研究计划
  • 研究期限:2016年01月01日 至 2018年12月31日
  • 中文关键词: Tβ4;HIF-1α;大鼠;血管;新生
  • 英文关键词:Thymosin β4;Hypoxia inducible factor-1α;Signal pathway;Gene Therapy;Coronary Heart Disease

项目摘要

中文摘要

目前冠心病的各种治疗方法均不十分理想。我们前期研究证实血管内皮生长因子(VEGF)转染骨髓间充质干细胞(MSCs)移植入心梗区可促进血管新生和改善心功能,为避免单一生长因子作用生成的血管存在不稳定和易渗漏问题,进一步将缺氧诱导因子(HIF)转染MSCs,通过促进HIF表达来调节下游多种生长因子共同作用以生成成熟稳定的新生血管,然而我们同时发现HIF表达存在时效较短的问题。胸腺素β4(Tβ4)是强有力的促进冠脉生成和稳定的刺激因子,有研究表明Tβ4可通过稳定HIF-1α来影响VEGF的表达而促进血管新生,然而其具体机制不明。本课题拟通过外源性Tβ4干预MSCs,观察其对HIF-1α表达的调控作用并探讨可能的机制,同时将转染Tβ4的MSCs移植入大鼠心梗区,观察体内其与HIF-1α和VEGF之间的关系,以及对心梗区血管新生的作用和心梗后心功能的影响。为Tβ4治疗冠心病提供理论依据和实验基础。

英文摘要

Coronary heart disease (CHD) has become one of the most serious diseases to jeopardize human health in recent years in our country. But present traditional treatments for CHD such as medicine, interventional therapy or surgery have some disadvantages. Our previous experiment has confirmed that transplantation of bone marrow stromal cells (MSCs) transferred with vascular endothelial growth factor (VEGF) into myocardial infarction area can promote angiogenesis and improve cardiac function. Because the new blood vessels induced by a single growth factor have the problem of instability and leakage, we then tried to transferred Hypoxia-inducible factor (HIF) gene into MSCs to adjust its downstream growth factors acting together to generate mature and stable neovascularization by promoting the expression of HIF. However, we also found the expression of HIF was time limited. Thymosin β4 (Tβ4) is a powerful stimulating factor for coronary vessel generation and stability. It was showed that Tβ4 can improve the expression of VEGF and promote angiogenesis by stabilizing HIF-1α, but its exact mechanism is unclear. So here we plan to use exogenous Tβ4 intervening MSCs to observe its effect to HIF-1α and explore its possible mechanism. Simultaneously, we transplant MSCs transferred with Tβ4 gene into rat myocardial infarction area to observe the relation between Tβ4, HIF-1α and VEGF, and examine its effect to angiogenesis in infarcted area and cardiac function after myocardial infarction. This may be helpful for Tβ4 treatment of coronary heart disease by providing a theory basis and experimental foundation.

评估说明

    国家自然科学基金项目“Tβ4稳定HIF-1α功能的信号通路及其促进大鼠心梗后血管新生的作用机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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