中枢神经系统（CNS）纤维瘢痕是轴突再生的主要障碍之一，但最新研究显示其是由多种细胞构成的、可能具有多重作用的复杂结构。其如何形成，作用如何？亟待阐明。Shh和Sirt1调控外周组织纤维化，但是否调控CNS纤维瘢痕的形成，尚待研究。课题组前期已在国际上率先证明Sirt1是Shh通路上游调节剂，但如何调控，亟待研究。Sirt1能调控TGF-β1/Smad2/3而影响外周组织纤维化，其是否通过调控TGF-β1/Smad2/3而调节Shh信号，从而调控CNS纤维瘢痕的形成，尚不清楚。因此，本课题采用基因转染等技术以纤维瘢痕和脑膜来源成纤维细胞和MCAOI/R模型大鼠为研究对象，系统地从体内外探讨Sirt1、TGF-β1/Smad2/3和Shh相互作用及对纤维疤痕形成的影响，以阐明纤维瘢痕的形成通过Sirt1→TGF-β1/Smad2/3 →Shh途径调控，为开发设计新药干扰纤维瘢痕奠定实验基础。

Fibrotic scars of the central nervous system (CNS) is one of the main obstacles for axon regeneration, but recent studies have shown that it is a complex structure composed of many kinds of cells and may have multiple functions. It is urgent to be clarified how it forms and what role it plays. Shh and Sirt 1 regulate the fibrosis of peripheral tissue, but it remains to be studied whether they regulate the formation of CNS fibrotic scars. Our previous study had firstly demonstrated in the world that Sirt1 is the upstream regulator of Shh pathway.However, it needs to be studied urgently how Sirt1 regulates Shh. Sirt1 can control peripheral tissue fibrosis via regulating TGF-β1/Smad2/3.It remains unclear whether Sirt1 can regulate Shh signal by regulating TGF-β1/Smad2/3 and thereby regulate the formation of CNS fibrotic scars. Therefore, with a number of techniques such as RNAi and gene transfection, we study systematically crosstalk of Sirt1,TGF-β1/Smad2/3 and Shh signal and its effects on formation of fibtotic scars in vivo and in vitro with fibrotic scars and meningeal-derived fibroblasts and MCAOI/R model rats as research objects in order to clarify fibrous scar formation via regulating of Sirt1→TGF-β1/Smad2/3 →Shh pathway,which will provide firmly experimental basis toward the development of next generation therapeutics for new drugs.