HIF-1α抑制PTEN基因调节人脐血干细胞修复HIBD大鼠突触功能的机制研究

项目名称： HIF-1α抑制PTEN基因调节人脐血干细胞修复HIBD大鼠突触功能的机制研究

项目编号： No.81672248

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 代英

作者单位： 重庆医科大学

项目金额： 25万元

中文摘要： 新生儿缺氧缺血性脑损伤(HIBD) 常留下不同程度的认知功能障碍，严重危害儿童的身心健康，给家庭和社会带来沉重负担。间充质干细胞的功能重建作用为治疗HIBD开辟了新途径 ，但其修复认知的作用机制却并不清楚。该课题是基于既往研究证实缺氧可激活骨髓间充质干细胞缺氧诱导因子-1α（HIF-1α）下游信号并调节突触可塑性的合理深入，在前期工作证实H IF-1α的神经保护作用是通过调节AMPA的Glu2R的基础上，把握PTEN在兴奋性突触功能研究的最新动态，以HIF-1α稳定剂CoCl2模拟缺氧状态，通过激活HIF-1α，研究更具临床价值的人脐血间充质干细胞旁分泌参与AMPA/Glu2R介导的HIBD新生大鼠突触功能修复机制。本课题首次提出激活HIF-1α可通过抑制PTEN直接参与突触可塑性调节，同时为探讨人脐血间充质干细胞旁分泌机制调节突触功能提供了新思路，它将为新生期缺氧缺血性脑损伤的治疗提供新

中文关键词： 缺氧缺血脑损伤；人脐血干细胞；；缺氧诱导因子-1α；PTEN；突触可塑性

英文摘要： Hypoxic-ischemic brain damage (HIBD) children often have varying degrees of cognitive dysfunction, which not only do serious harm to the health of children but also bring a heavy burden to families and the community. The role of functional reconstruction in Mesenchymal stem cells provide a new way for the treatment of HIBD. However, its mechanism of restoration cognition is not clear yet. The subject is based on previous studies demonstrated that hypoxia activated hypoxia-inducible factor -1α (HIF-1α) signaling system in bone marrow mesenchymal stem cells and regulated synaptic plasticity. Our previous studies already confirmed that the neuroprotective effect of HIF-1α is related with regulating AMPA Glu2R. Considering the recent study focusing on PTEN in excitatory synaptic function, now we are going to using HIF-1α stabilizer CoCl2 to activate HIF-1α in human umbilical cord blood mesenchymal stem cells and study the AMPA-mediated repairing mechanisms in synaptic function of HIBD rats. To our knowledge it is the first time to study the directly inhibition role on PTEN by activating HIF-1α involved with regulating synaptic plasticity. And it is the first time to explore the paracrine mechanism of human umbilical cord blood-derived mesenchymal stem cells in regulating synaptic function. Our study will provide a new idea and new ways in neonatal hypoxic-ischemic brain injury treatment.

英文关键词： Hypoxic-ischemic brain damage;human umbilical cord blood mesenchymal stem cells;hypoxia-inducible factor -1α;PTEN;synaptic plasticity