正常、退行性病变、脱髓鞘小鼠的脊髓内Mts1/S100A4表达及作用比较(英文)

The calcium-binding protein Mts1/S100A4 in normal, degenerating and demyelinated spinal cord of the adult mouse

目的: 研究正常、退行性病变以及脱髓鞘小鼠脊髓内Mts1/S100A4蛋白的表达模式,及其对胶质细胞反应的影响。方法: 以野生型和 Mts1/S100A4 基因敲除型小鼠为试验动物, 采用背根损伤、坐骨神经损伤、溴乙啶局部微量注射的方法复制退行性病变及脱髓鞘脊髓动物模型,应用免疫荧光技术,检测S100A4、GFAP、NG2、Mac1的表达情况。结果: 野生型小鼠脊髓内,仅白质星型胶质细胞表达S100A4蛋白,且主要分布于Lissauer束; 背根或坐骨神经损伤后,白质星形胶质细胞内的S100A4及GFAP表达上调,野生型与S100A4基因敲除小鼠GFAP 表达量无显著差异; 溴乙啶注射7d后, 野生型小鼠脊髓脱髓鞘区域内见S100A4呈云雾状分布,胶质细胞反应局限于注射侧,并且形成清晰的胶质瘢痕, 而S100A4基因敲除小鼠则未见上述病理变化。结论: S100A4蛋白在小鼠脊髓内的表达模式与大鼠相似;退行性变的脊髓内,细胞内上调的 S100A4 蛋白并不影响胶质细胞的反应; 脱髓鞘脊髓内,细胞外的S100A4蛋白明显影响胶质细胞反应,包括胶质瘢痕的形成。

Objective： To investigate the expression pattern of Mtsl/S100A4 in mouse spinal cord;to investigate the effects of Mtsl/S100A4 on glial cell responses. Method： The study was carried out on Mtsl/S100A4 wild type and knock-out mice. The degenerative spinal cord model was established by dorsal root or sciatic nerve injury. The de- myelinated spinal cord model was established by ethidium bromide injections. Then the expressions of S100A4, GFAP,NG2 and Macl were measured. Result： The expressions of Mtsl/S100A4 in mice spinal cord were similar to that in rats. In WT mice this protein expressed in a thin layer of fiber bundles in the tract of Lissauer, and in white matter astrocytes. There was intracellular up-regulation of Mtsl/S100A4 in white matter astrocytes of WT mice after dorsal root or sciatic nerve injury, with no difference in glial cell response between WT and KO mice. However, 7 days after ethidium bromide injection, in WT mice, the astroglial reaction was restricted on operated side, where a distinct glial scar had formed. While in KO mice, no distinct glial scar formed in demyelinated area. Conclusion： Mtsl/S100A4 expression in mouse spinal cord is similar to the pattern as in rats; intracellular Mtsl/ S100A4 up-regulation does not affect glial responses in degenerative spinal cord;the presence of extracellular Mtsl/ S100A4, which entered the spinal cord after ethidium bromide induced demyelination, markedly affects the glial cell responses in demyelinative spinal cord, including glial scar formation.