高荣 祖丽皮亚·达木拉

【摘要】 目的：探讨手足口病患儿DLL4/Notch信号通路相关蛋白的表达及意义。方法：选择2018年3月-2019年11月本科收治的手足口病患儿86例，其中轻症患儿76例（普通组），重症患儿10例（重症组），同期选择在本院体检的健康小儿86例作为对照组。比较三组外周血DLL4、Notch1 mRNA表达水平与血清IL-6、IL-8、TNF-α表达水平，并进行相关性分析。结果：重症组住院天数、发热天数均长于普通组，休克、呼吸衰竭、EV71感染发生率均高于普通组，差异均有统计学意义（P<0.05）。重症组与普通组的血清IL-6、IL-8、TNF-α水平均高于对照组，重症组的血清IL-6、IL-8、TNF-α水平均高于普通组，差异均有统计学意义（P<0.05）。重症组与普通组外周血DLL4、Notch1 mRNA相對表达水平均高于对照组，重症组外周血DLL4、Notch1 mRNA相对表达水平均高于普通组，差异均有统计学意义（P<0.05）。在手足口病患儿中，Pearson分析显示DLL4、Notch1表达水平与IL-6、IL-8、TNF-α存在相关性（P<0.05）。结论：手足口病患儿伴随着DLL4/Notch信号通路相关蛋白表达的激活，可诱发大量炎症因子的释放，与患者的病情存在相关性。

【关键词】 手足口病 DLL4/Notch信号通路 炎症因子 病情 相关性

Expression and Significance of DLL4/Notch Signaling Pathway Related Proteins in Children with Hand-foot-mouth Disease/GAO Rong， Zulipiya Damula. //Medical Innovation of China， 2021， 18（12）： 0-084

[Abstract] Objective： To investigate the expression and significance of DLL4/Notch signaling pathway related proteins in children with hand-foot-mouth disease （HFMD）. Method： A total of 86 children with HFMD admitted to our hospital from March 2018 to November 2019 were selected， including 76 children with mild disease （normal group） and 10 children with severe disease （severe group）， and 86 healthy children with physical examination in our hospital during the same period were selected as the control group. The mRNA expression levels of DLL4 and Notch1 in peripheral blood of three groups were compared with the expression levels of IL-6， IL-8 and TNF-α in serum， and the correlation analysis was conducted. Result： The hospitalization days and fever days in the severe group were longer than those in the normal group， and the incidence of shock， respiratory failure and EV71 infection were higher than those in the normal group， the differences were statistically significant （P<0.05）. Serum levels of IL-6， IL-8 and TNF-α in the severe group and normal group were higher than those in the control group， serum levels of IL-6， IL-8 and TNF-α in the severe group were higher than those in the normal group， the differences were statistically significant （P<0.05）. The mRNA relative expression levels of DLL4 and Notch1 in peripheral blood of the severe group and the normal group were higher than those of the control group， and the mRNA relative expression levels of DLL4 and Notch1 in peripheral blood of the severe group were higher than those of the normal group， the differences were statistically significant （P<0.05）. In children HFMD， Pearson analysis showed that the expression levels of DLL4 and Notch1 were correlated with IL-6， IL-8， TNF-α （P<0.05）. Conclusion： The activation of DLL4/Notch signaling pathway related protein expression in children with hand-foot-mouth disease can induce the release of a large number of inflammatory factors， which is correlated with the patients condition.

[Key words] Hand-foot-mouth disease DLL4/Notch signaling pathway Inflammatory factors Condition

Correlation

First-authors address： Childrens Hospital of Xinjiang Uygur Autonomous Region， Urumqi 830054， China

doi：10.3969/j.issn.1674-4985.2021.12.019

手足口病（hand-foot-mouth disease， HFMD）是由腸道病毒引起婴幼儿常见急性传染病，以疱疹、发热、口腔疼痛为主要临床特征的传染病[1]。其主要的病原体为柯萨奇病毒A组16型（coxsackie virus， CA16）或肠道病毒71型（enterovirus 71， EV71），其中EV71感染具有极强的传染性[2-3]。轻度感染患儿预后良好;重度感染患儿多伴随着神经系统并发症，包括脑干脑炎、无菌性脑膜炎、神经源性肺水肿、急性弛缓性麻痹，多为EV71感染引起，具有一定的致死率[4]。有研究报道显示EV71具有亲神经性，使得手足口病患儿容易出现脑炎，导致疾病恶化。DLL4/Notch信号通路是进化上比较保守的跨膜蛋白家族，主要由配体、受体、结合蛋白、调节分子、效应物等组成[5]。人体共有多种Notch配体（DLL1、DLL3、DLL4、Jagged1）和多种Notch受体（Notch1、Notch2、Notch3、Notch4）等，其中Notch1属于Ⅰ型跨膜蛋白，当胞外区域与配体结合后，Notch受体被解聚素和金属蛋白酶水解，跨膜区和胞内区由γ-分泌酶复合体催化为Notch胞内区，然后进入胞核后，可水解成组蛋白去乙酰化酶、核受体辅阻遏物2等因子，从而发挥生物学调节作用[6]。……