核因子-κB/抑制蛋白-κB信号通路介导的激素敏感型单纯性肾病患儿病毒基因反式激活

Viral Transactivation of Transcription in Steroid Responsive Simple Nephrotic Syndrome Mediated by Nuclear Factor-Kappa B/Inhibitor Protein-Kappa B Signal Pathway

目的研究核因子-κB(NF-κB)/抑制蛋白-κB(IκB)信号通路在激素敏感型单纯性肾病(SRSNS)患儿病毒基因反式激活中的作用。方法采用电泳迁移率改变实验、逆转录-聚合酶链反应(RT-PCR)和酶标记免疫吸附分析法(ELISA)分别测定SRSNS、肾炎性肾病、继发性肾小球疾病、毛细支气管炎和正常儿童外周血单个核细胞(PBMCs)NF-κB活性、呼吸道病毒基因和血浆病毒抗体;同时采用Western blot和ELISA分别检测SRSNS和正常儿童IκBα蛋白质表达和血浆IL-8水平。结果与SRSNS缓解期和其他组比较,SRSNS活动期组NF-κB活性明显增加。NF-κB活性与呼吸道病毒检出阳性率呈正相关趋势。SRSNS活动期血浆IL-8水平增高,且与NF-κB活性呈正相关(r=0.88 P<0.001)。SRSNS活动期患儿IκBα蛋白质明显低于SRSNS缓解期和正常儿童,IκBα蛋白质水平与NF-κB活性呈负相关(r=-0.884 P<0.05)。结论NF-κB/IκB信号通路介导的病毒基因反式激活过程,可能是呼吸道病毒触发SRSNS的主要机制之一。

Objective To investigate the role of nuclear factor kappa B（ NF - κB）/inhibitor protein - kappa B（IκB） signal pathway in viral transactivation of transcription in steroid responsive simple nephrotic syndrome（SRSNS）. Methods Children with SRSNS（including active stage and remissive stage） were examined, and were compared to children with nephritic nephrosis, secondary glomerular diseases, bronchiolitis and healthy children. Electro - mobility shift assays, reverse transcription - polymerase chain reaction （ RT - PCR） and enzyme linked immunosorbent assay（ELISA） were used to detect the activity of NF - κB, the gene expression of respiratory tract viruses （ including respiratory syncytial virus and influenza virus） in peripheral blood mononuclear cells（PBMCs） and the levels of viral antibody in plasma, respectively. The protein levels of IκBα and IL - 8 were measured through Western blot and ELISA in SRSNS at active stage and healthy children. Results Compared with SRSNS at remissive stage and other groups, the activity of NF - κB in SRSNS at active stage was much higher. And there was a positive linear correlation trend between the activity of NF- κB and the gene expression of respiratory tract viruses in SRSNS at active stage. With healthy children, the level of IL - 8 in plasma from SRSNS at active stage was significantly incre.ased. There was a positive correlation between the activity of NF-κB and the level of IL- 8（ r = 0.88 P 〈 0.001 ）. The protein level of IκBα in children with SRSNS at active stage was much lower than that of healthy children, and a linear negative correlation between the activity of NF-κB and the protein level of IκBα（ r = 0. 884 P 〈 0.05 ）. Conclusions Viral transactivation of transcription is mediated by NF-κB/IκB signal pathway, which may play an important role in the pathogenesis of SRSNS triggered by respiratory tract viruses.