Toll样受体3在呼吸道合胞病毒肾病大鼠发病中的作用研究

Activation of TLR3 Pathway in the Pathogenesis of Nephrotic Syndrome Induced by Respiratory Syncytial Virus in Rat Model

目的动态观察Toll样受体3(Toll-like receptor 3,TLR3)信号通路在呼吸道合胞病毒(RSV)肾病大鼠肾组织中的表达变化,探讨其在RSV肾病发病中的作用。方法同时以6×106空斑形成单位RSV经鼻腔滴入及腹腔注射接种SD大鼠,建立RSV大鼠肾病模型,以未予处理的正常组为对照。分别于接种后4、14、30 d(RSV4、RSV14、RSV30)处死大鼠后取肾组织,观察其形态学改变。间接免疫荧光及实时荧光定量RT-PCR比较各组大鼠肾组织上TLR3、核因子-κB(NF-κB)及白介素13(IL-13)蛋白及基因表达变化。结果 RSV可致大鼠尿蛋白增加,肾小球上皮细胞足突融合类似人类微小病变型肾病综合征。RSV4及RSV14组大鼠肾组织TLR3、NF-κB及IL-13表达较正常对照组增高。RSV30组大鼠肾组织TLR3、NF-κB及IL-13表达降低,与正常对照组比较无明显差异。结论 TLR3信号通路可能在RSV肾病发生发展早期阶段起重要作用。

Objective To explore the activation of toll-like receptor 3(TLR3) pathway on the process of respiratory syncytial virus(RSV) induced nephropathy.Methods SD rats were inoculated intranasally and intraperitoneally with 6×106 plaque forming unit(PFU) RSV and sacrificed on days 4,14,30 postinoculation(RSV4,RSV14 and RSV30).The normal rats without intervention were set as control.Renal tissues were obtained,and the morphological changes were studied.The expressions of TLR3,NF-κB and IL-13 in the rats’ kidney were measured with real-time quantitative RT-PCR,and indirect IF staining.Results After the inoculation of RSV,the rats had proteinuria and the fusion of foot processes of glomerular epithelial cells,resembling human minimal changed nephrotic syndrome(MCNS).The expressions of TLR3,NF-κB and IL-13 in renal tissues increased obviously at Day 4 and Day 14 postinoculation,the differences were significant when compared with normal control rats(P0.05).Conclsuion TLR3 signal pathway may play an important role in early stage of RSV nephropathy.