肿瘤坏死因子-α对少突胶质前体细胞的影响及其机制的研究

The effect of TNF-alpha on oligodendrocyte progenitor and its mechanism

目的探讨肿瘤坏死因子-α(TNF-α)对少突胶质前体细胞(OPC)的作用及机制,为脑室周围白质软化(PVL)的治疗提供策略。方法将分离纯化的OPC分为空白对照组、TNF-α组、肿瘤坏死因子受体1(TNFR1)抗体组,将50ng/mL TNF-α作用于TNF-α组、TNFR1抗体组,免疫荧光化学检测OPC的分化情况,四甲基偶氮唑盐(MTT)法检测3组细胞的相对活力,RT-PCR检测细胞TNFR1的mRNA水平的表达情况。结果与空白对照组和TNFR1抗体组相比,TNF-α组OPC的细胞活力明显下降(P<0.05),并且不能沿着少突胶质谱系细胞进行分化,即分化为原少突胶质细胞。TNF-α组TNFR1的mRNA表达明显的上调,空白对照组和TNFR1抗体组的mRNA表达无明显的变化。结论 TNF-α主要通过TNFR1引起OPC的凋亡,抑制OPC分化。

Objective To explore the effect of tumor necrosis factor-α（TNF-α） on the oligodendrocyte progenitor,and provide a strategy for the treatment of Periventricular leukomalacia. Methods The purified oligodendrocyte progenitor were divided into three groups：blank control group,TNF-α group and anti- TNFR1 group. TNF-α group and anti- TNFR1 group were treated with TNF-α, the differentiation of OPC were detected by immunocytochemica] method, the relative viability of cells in three groups were measured by MTT assay,the levels of TNFR1 gene was observed with RT-PCR. Results The relative cell viability of TNF-α group was significantly decreased（P〈0.05） and did not turn into cells called prooligodendrocyte. TNF-α group increased the expression of TNFR1 mRNA,and there were no differences in the expression of TNFR1 mRNA between the blank control group and anti- TNFR1 group, Conclusion TNF-α could induced OPC apoptosis and inhibited the differentiation of OPC through the TNFR1.