线粒体融合蛋白2（Mfn2)抑制胶质细胞活化促进脊髓损伤修复研究

Reactive astrocytes and many kinds of secreted extracellular matrix are major contributors to the glial scar that is a physical and chemical barrier to axonal regeneration. Besides inducing mitochondrial fusion, mfn2 plays important roles in signal transduction, energy metabolism and proliferation and apoptosis. It was reported that overexpression of mfn2 overtly suppressed VSMC proliferation in culture, and the anti-proliferative effect was mediated by inhibition of ERK/MAPK signalling and subsequent cell-cycle arrest. Our previous studies suggested that mfn2 expression was markedly reduced after spinal cord injury. And after mfn2 was transfected in vitro, AS proliferation was inhibited, but the mechanism remains elucidated. We presume that mfn2 should be an important negative factor to glia scar formation and be benefit for spinal cord regeneration. So we explore why mfn2 has such functions in our next research in vivo and in vitro in order to find a new target for treatment of spinal cord injury.

脊髓损伤（SCI）活化增殖并分泌多种细胞外基质共同构成胶质瘢痕是影响轴突再生及功能恢复的重要原因之一。抑制AS活化增殖形成胶质瘢痕有利于轴突再生。近年来研究发现线粒体融合蛋白-2（Mfn2）能够有效抑制细细胞周期相关蛋白使血管内皮细胞停留在G0/G1期，阻止其异常增生。Mfn2在抑制肿瘤细胞和血管平滑肌细胞生长、诱导细胞凋亡发挥重要作用。前期我们已证实，Mfn2在SCI后表达明显降低，导入外源性Mfn2能明显抑制AS增殖，Mfn2抑制胶质细胞活化、增值中的作用国内外尚无报导。我们推测"Mfn2可能是一种重要抑制胶质细胞活化和的胶质瘢痕形成负调控因子",对脊髓损伤修复产生积极作用。为证实假说，本课题我们将从体外和体内阐明Mfn2抑制星形胶质细胞活化及脊髓损伤后抑制胶质瘢痕形成的分子机制，为脊髓损伤修提供新的靶点。

脊髓损伤（SCI）活化增殖并分泌多种细胞外基质共同构成胶质瘢痕是影响轴突再生及功能恢复的重要原因之一。抑制AS 活化增殖形成胶质瘢痕有利于轴突再生。近年来研究发现线粒体融合蛋白2（Mfn2）能够有效抑制细细胞周期相关蛋白使血管内皮细胞停留在G0/G1 期，阻止其异常增生。Mfn2在抑制肿瘤细胞和血管平滑肌细胞生长、诱导细胞凋亡发挥重要作用。前期我们已证实，Mfn2 在SCI后表达明显降低，导入外源性Mfn2 能明显抑制AS 增殖，Mfn2 抑制胶质细胞活化、增值中的作用国内外尚无报导。我们推测"Mfn2 可能是一种重要抑制胶质细胞活化和的胶质瘢痕形成负调控因子",对脊髓损伤修复产生积极作用。在体外细胞实验我们发现，在体外机械损伤和血清刺激诱导的星形胶质细胞活增殖过程中Mfn2在基因和蛋白水平的含量随着时间的推移均呈下降趋势；过表达Mfn2能明显抑制星胶活化相关蛋白PCNA和GFAP的表达；表达Mfn2能明显抑制星胶活化相关蛋白GFAP的表达及周期分裂活化因子PCNA,CyclinD1表达,抑制细胞周期进展；过表达Mfn2通过抑制星形胶质细胞活化而延缓了划痕愈合；过表达Mfn2通过抑制as-Raf1-ERK1/2蛋白磷酸化阻碍增值活化通路，抑制细胞周期进展，下调增值活化因子（PCNA,CyclinD1）抑制星形胶质细胞增值。本课题从体外实验阐明Mfn2 抑制星形胶质细胞活化，为体内实验奠定了良好的基础，为脊髓损伤修提供新的思路。