TLRs-NF-kB信号通路在重症手足口病发病中的作用机制研究

Study on the Role and Mechanism of TLRs-NF-kB Signaling Pathway in Severe Hand,foot and Mouth Disease

目的探讨Toll样受体-核转录因子-κB(TLRs-NF-κB)信号通路在重症手足口病发病机制中的作用。方法回顾性分析2014年1月至2019年6月苏州大学附属儿童医院感染科及重症医学科收治重症手足口病患儿96例(重症组),普通型手足口病患儿102例(普通组)以及健康对照组儿童20例(健康组),观察2组手足口病患儿的临床表现及病毒检测结果;酶联免疫吸附法(ELISA)检测3组血清细胞因子血清白细胞介素-6、-10(IL-6、IL-10),γ-干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)及核转录因子-κB(NF-κB)水平,采用流式细胞术检测3组TLRs细胞限制存在型(TLR2、TLR4)阳性细胞百分比。结果重症组肠道病毒71型(EV71型)感染阳性率高于普通组(62.50%vs.25.49%,P<0.05);与健康组比较,重症组和普通组患儿血清IL-10、IL-6、IFN-γ、TNF-α、NF-κB水平以及TLR2、TLR4阳性细胞百分比均升高(P<0.05),且重症组高于普通组(P<0.05)。结论重症手足口病患儿机体免疫紊乱较为严重,血清IL-10、IL-6、IFN-γ、TNF-α、NF-κB以及TLR2、TLR4阳性细胞百分比均升高,TLRs-NF-kB信号通路在疾病的发病中的发挥了重要的作用。

Objective To investigate the role of TLRs-NF-kB signaling pathway in the pathogenesis of severe hand,foot and mouth disease.Methods From January 2014 to June 2019,Totally 96 cases of children with severe hand,foot and mouth disease(severe group),102 cases of common hand,foot and mouth disease(normal group)and 20 cases of healthy control group(health group)were admitted to the department of infection and intensive care department of children's hospital affiliated to soochow university.Serum levels of cytokines IL-10,IL-6,IFN-γ,TNF-α,NF-κB were detected by ELISA,and the percentage of positive TLR2 and TLR4 were detected by flow cytometry.Results the positive rate of EV71 infection in the severe group was higher than that in the normal group(62.50%vs.25.49%,P<0.05).Serum levels of IL-10,IL-6,IFN-γ,TNF-α,NF-κB as well as the percentage of TLR2 and TLR4 positive cells in both the severe and normal groups were higher than those in the health group(P<0.05),and the severe group were higher than the common group(P<0.05).Conclusion The children with severe hand,foot and mouth disease have serious immune disorders,and the serum levels of IL-10,IL-6,IFN-γ,TNF-α,NF-κB,as well as the percentage of TLR2 and TLR4 positive cells all increased.The TLRs-NF-kB signaling pathway plays an important role in the pathogenesis of the disease.