朊病毒感染与内源性嘌呤受体P2X7相互关系的研究

摘要

目的 明确朊病毒感染对P2X7受体的影响,并评价P2X7受体活化对朊病毒复制的作用.方法 Western Blot检测朊病毒毒株263K感染的仓鼠、ME7和139A感染的C57 BL/6小鼠和稳定感染羊瘙痒因子Chandler株的小鼠神经细胞系SMB-S15中P2X7受体的蛋白表达,并检测P2X7激活剂ATP对SMB-S15细胞中朊病毒PrPSc含量的影响.结果 朊病毒感染的动物及细胞模型中,P2X7受体表达降低(P＜0.05),ATP孵育4d可降低SMB-S15细胞中PrPSc的含量.结论 P2X7信号通路活化对朊病毒感染细胞具有一定的保护作用.嘌呤信号通路有望为抗朊病毒治疗提供新的靶点.%Objective To assess the impact of prion infection on purinoceptor P2X7,and evaluate the role of P2X7 activation during prion replication.Methods The expression of P2X7 in scrapie strain 263K-infected hamsters,strains 139A and ME7-infected mice and prion infected cell line SMB-S15 analyzed by Western Blot and the influence of P2X7 activation on the level of PrPSc in SMB-S15 cells after 4-day-incubation with ATP was observed.Results P2X7 expression was down-regulated by prion infection and activation of P2X7 by ATP decreased the amount of PrPSc in SMB-S15 cells.Conclusions P2X7 receptor and its downstream signaling pathways could play important protective roles during prion infection,which highlights its therapeutic potential in prion diseases.