ystatin F 基因敲除加重 cuprizone 模型髓鞘脱失的分子机制

Objective: Molecular mechanism of cys F gene ablation exacerbating demyelination in cuprizone model. Methods: C57BL/6J wild-type mice, cystatin F knockout(cys F KO) mice and cathepsin C overexpression (Cat C OE) mice were treated 0.2% cuprizone. Real-time PCR and ELISA were used to analyze the expression of CXCL2.Immunohistochemical staining were to observe remaining myelin and oligodendrocyte.In vitro, primary cultured glial cells were co-incubated with recombinant cathepsin C(Cat C) for 24 hours to analyze the expression of CXCL2 by real-time PCR and ELISA. Results: The CXCL2 expression in Cys F KO mice was significantly higher than wild type mice. Significantly more CD45 positive cells were found in cys F KO mice,compared with wild type mice, In vitro ,Cat C could induce CXCL2 in cultured glia in a dose-dependent manner. The remaining myelin area ratio in Cat C OE mice was significantly less than wild type mice. However, CD45 positive cells in Cat C OE mice was significantly more than wild type mice. Conclusions: Ablation of cystatin F results in loss of its inhibition of cathepsin C activity, which could up-regulate the expression of CXCL2 and lead to more inflammatory cells infiltration, finally aggravates the position of demyelination.