TGF-β1调控大鼠脑缺血后内源性神经干细胞增殖分化及机制研究

TGF-beta1 plays an important role in the neuroprotection and neurorestoration after cerebral ischemia. However, the function and mechanism of TGF-beta1 on the proliferation and differentiation of endogenous NSCs after cerebral ischemia is still unknown. In preliminary work, we have found that TGF-beta1 can promote proliferation of NSCs in vitro, which in physiological state, and protect neural function after cerebral ischemia in rats. This study intends to set up cerebral ischemia models in vivo and in vitro, using TGF-beta1 knockout rats and primary cultured hippocampal NSCs, and research the laws and characteristics of proliferation and differentiation of endogenous NSCs after cerebral ischemia in vivo and in vitro under the intervention of TGF-beta1, and explore the function of Smads, Wnt/beta-catenin and Notch signaling pathways in TGF-beta1 regulating proliferation and differentiation of endogenous NSCs, with the aid of siRNA, immunofluorescence, RT-PCR, western blot and laser confocal. The results will verify that TGF-beta1 could promote proliferation and differentiation of endogenous NSCs after cerebral ischemia, also clarify whether TGF-beta1 influence the proliferation and differentiation of NSCs through Smads, Wnt/beta-catenin or Notch signaling pathways. This study will provide theoretical basis for precise regulating proliferation and differentiation of endogenous NSCs and neural functional reconstruction after cerebral ischemia.

TGF-β1在脑缺血后神经保护及神经修复中发挥着重要作用，但TGF-β1对脑缺血后内源性神经干细胞（NSCs）增殖分化的调控及分子机制尚不清楚。申请者前期工作发现TGF-β1可促进生理状态下体外培养的NSCs增殖，对脑缺血后大鼠的神经功能有保护作用。本研究拟利用TGF-β1基因敲除大鼠和原代培养的海马NSCs建立活体和离体脑缺血模型，借助siRNA、免疫荧光、RT-PCR、免疫印迹和激光共聚焦成像等技术，研究TGF-β1在离体和活体脑缺血模型中调控内源性NSCs增殖分化的特点与规律，研究Smads、Wnt/β-catenin和Notch信号通路在TGF-β1调控内源性NSCs增殖分化中的作用。证实TGF-β1可促进脑缺血后内源性NSCs的增殖分化，并阐明分子机制。本课题将为精准调控脑缺血后内源性NSCs增殖分化的过程，实现神经功能重建提供重要理论依据。

TGF-β1在脑缺血后神经保护及神经修复中发挥着重要作用，但TGF-β1对脑缺血后内源性神经干细胞（NSCs）增殖分化的调控及分子机制尚不清楚。申请者前期工作发现TGF-β1可促进生理状态下体外培养的NSCs增殖，对脑缺血后大鼠的神经功能有保护作用。本研究拟利用TGF-β1基因敲除大鼠和原代培养的海马NSCs建立活体和离体脑缺血模型，借助siRNA、免疫荧光、RT-PCR、免疫印迹和激光共聚焦成像等技术，研究TGF-β1在离体和活体脑缺血模型中调控内源性NSCs增殖分化的特点与规律，研究Smads、Wnt/β-catenin和Notch信号通路在TGF-β1调控内源性NSCs增殖分化中的作用。证实TGF-β1可促进脑缺血后内源性NSCs的增殖分化，并阐明分子机制。本课题将为精准调控脑缺血后内源性NSCs增殖分化的过程，实现神经功能重建提供重要理论依据