Wnt5a信号通路调控NRTI引起的小脑神经炎症的研究  

Study on Cerebellum Neuroinflammation Induced by NRTI Regulation with Wnt5a Signal Channel

作　　者：耿明星 吴婷[1] 张娟[1] 杨意[1] 刘小康[1] 舒建洪[1] GENGMingxing WUTing ZHANGJuan YANGYi LIUXiaokang SHUJianhong(College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China)

机构地区：[1]浙江理工大学生命科学学院,杭州310018

出　　处：《浙江理工大学学报（自然科学版）》2016年第6期922-927,共6页Journal of Zhejiang Sci-Tech University(Natural Sciences)

基　　金：国家科技重大新药创制项目(2012ZX09102301);浙江省自然科学基金项目(LY13H090015)

摘　　要：分别用NRTI类药物AZT(100mg/kg)和3TC(50mg/kg)对C57BL/6小鼠进行2、5、14d的处理,并于药物处理结束时采集小鼠小脑。通过Western blotting检测两种药物处理不同时间后小脑中炎症因子IL-1β,TNF-α和IL-6的表达水平,观察到炎症因子在小脑中都显著性增加。然后通过HE染色研究NRTI作用5d对小脑病变的影响,组织形态学分析表明,NRTI药物作用5d未引起小脑发生显著病变。通过Western blotting检测到小脑中NRTI可明显上调Wnt5a,提示NRTI可能激活Wnt5a,再利用Wnt5a的特异性拮抗剂BOX5来抑制Wnt5a,BOX5可以显著性降低NRTI诱导的炎症因子上调。因此,Wnt5a信号通路参与调控NRTI引起的小脑神经炎症。In this study,mice （C57Bl/6）were treated with NRTI drugs AZT （100 mg/kg,sc./days） and 3TC （50 mg/kg）for 2,5,or 14 days and cerebellum of mice was collected at the end of drug treatment.The expression level of inflammatory factors （IL-1β,TNF-αand IL-6 ）in cerebellum was detected with Western blotting under different treatment time of two drugs.The results show that IL-1β, TNF-αand IL-6 significantly increase in the cerebellum of NRTI-treated mice.Then,the effect of NRTI treatment for 5d on cerebellum lesion was investigated through HE dyeing.Histomorphology analysis shows that NRTI treatment for 5 d does not induce significant cerebellum lesion. Western blotting detection indicates that NRTI in cerebellum can significantly up-regulate Wnt5a,which prompts that NRTI may activate Wnt5a.Then,BOX5-a specific Wnt5a antagonist was applied to restrain Wnt5a. Western blotting result indicates that BOX5 can significantly reduce NRTI-induced inflammatory factor up-regulation.Thus,Wnt5a signal channel participates in regulating cerebellum neuroinflammation induced by NRTI.

关 键 词：NRTI 小脑 神经炎症 Wnt5a信号通路 BOX5 

分 类 号：R741.02[医药卫生—神经病学与精神病学]