智能SB-3CT-NPs 靶向抑制TBI后枢纽蛋白MMP-9的脑保护作用及机制

Our previous study demonstrates SB-3CT specific inhibitor of Hub-protein MMP-9 can attenuate the secondary damage to the brain and improve function recovery after traumatic brain injury (TBI) in the rat, but its mechanism is unclear. Therefore, in this study, the mechanical injury model for the co-cultured neurons and glial cells will be established to monitor the neurotransmitter release and inactivity, neuron damage and protection, cell apoptosis during the development of the TBI and the smart SB-3CT-NPs treatment, which will be also evaluated in the injured center and its penumbra of the brain in the rat fluid-percussion injury (FPI) model. In this applied project, our aim is to investigate the neuroprotective role of the smart SB-3CT-NPs and how it functions, from which we can reduce and even stop the secondary brain injury at the beginning of the TBI development and further minimize the damage of neurons and glial cells. Our findings will not only offer a new strategy for TBI treatment but also set up a study model for exploring other key gene roles in the TBI.

前期首次证实枢纽蛋白MMP-9特异性抑制剂SB-3CT能有效抑制创伤性脑损伤（TBI）后继发性脑损伤提高预后。但SB-3CT在TBI治疗中的分子作用机理却仍未明了。本课题拟应用"体外神经元/胶质细胞培养机械损伤模型"，动态研究脑损伤在智能SB-3CT-NPs治疗过程中递质释放调控与灭活、神经损伤与保护信号转导、细胞凋亡模式等多个环节的特点。另结合经典的"大鼠液压冲击伤（FPI）模型"，研究智能SB-3CT-NPs干预下损伤中心区及损伤半影区不同时间段上述递质释放－信号转导－细胞死亡调控环节的异同点及损伤动物病理组织，神经影像，功能行为变化。旨在证明通过智能SB-3CT NPs能有效启动TBI后内源性神经保护作用，并探索从源头上阻断继发性颅脑损伤进程的分子基础及起效机制，从而减少脑损伤后神经元及胶质细胞的死亡。本研究将为其它枢纽基因的探索提供研究模式，也为创伤后脑保护治疗提供一条新的研究策略

前期首次证实枢纽蛋白MMP-9特异性抑制剂SB-3CT能有效抑制创伤性脑损伤（TBI）后继发性脑损伤提高预后。但SB-3CT在TBI治疗中的分子作用机理却仍未明了。本课题拟应用"体外神经元/胶质细胞培养机械损伤模型"，动态研究脑损伤在智能SB-3CT-NPs治疗过程中递质释放调控与灭活、神经损伤与保护信号转导、细胞凋亡模式等多个环节的特点。另结合经典的"大鼠液压冲击伤（FPI）模型"，研究智能SB-3CT-NPs干预下损伤中心区及损伤半影区不同时间段上述递质释放－信号转导－细胞死亡调控环节的异同点及损伤动物病理组织，神经影像，功能行为变化。旨在证明通过智能SB-3CT NPs能有效启动TBI后内源性神经保护作用，并探索从源头上阻断继发性颅脑损伤进程的分子基础及起效机制，从而减少脑损伤后神经元及胶质细胞的死亡。本研究将为其它枢纽基因的探索提供研究模式，也为创伤后脑保护治疗提供一条新的研究策略。