Notch信号途径在儿童结核病中的作用研究

Role of the Notch signaling pathway in children with tuberculosis

摘要:

目的 研究Notch信号途径相关分子在儿童结核病中的表达情况，探讨其在儿童结核病发生中的作用。方法 选取2017年6月至2018年12月确诊的结核病患儿62例为病例组，另选取健康儿童64例为健康对照组，采集外周静脉血2 mL，应用实时荧光定量PCR法检测白细胞中Notch信号途径相关分子（受体Notch1~4，配体Jagged1、2和DLL1、3、4，下游靶基因Hes1和Hey1） mRNA水平。结果 与健康对照组相比，病例组患儿白细胞中Notch1、2和DLL4 mRNA水平均显著升高（P < 0.05）；病例组患儿白细胞中其他信号分子Notch3、4，Jagged1、2，DLL1、3，Hes1和Hey1 mRNA水平与健康对照组相比，差异均无统计学意义（P > 0.05）。结论 Notch1、2和DLL4 mRNA水平在结核病患儿中表达明显升高，但下游靶基因表达无明显变化，提示儿童结核菌感染后Notch1、2与其配体DLL4相互作用启动Notch信号途径，可能通过作用于其他靶基因在儿童结核病中发挥作用，需进一步研究探讨。

Abstract:

Objective To study the expression of molecules associated with the Notch signaling pathway in children with tuberculosis, as well as the role of this pathway in the pathogenesis of tuberculosis in children. Methods A total of 62 children who were diagnosed with tuberculosis from June 2017 to December 2018 were enrolled as the case group, and 64 healthy children were enrolled as the healthy control group. Peripheral venous blood samples with a volume of 2 mL were collected, and quantitative real-time PCR was used to measure the mRNA expression levels of the molecules associated with the Notch signaling pathway (receptors Notch1-4, ligands Jagged1/2 and DLL1/3/4, and downstream target genes Hes1 and Hey1) in leukocytes. Results Compared with the healthy control group, the case group had significant increases in the mRNA expression levels of Notch1, Notch2, and DLL4 in leukocytes (P < 0.05), while there were no significant differences in the mRNA expression levels of Notch3/4, Jagged1/2, DLL1/3, Hes1, and Hey1 between the two groups (P > 0.05). Conclusions There are significant increases in the mRNA expression of Notch1/2 and DLL4 in children with tuberculosis, while there are no significant changes in the expression of downstream target genes, suggesting that the Notch signaling pathway, which is activated by the interaction between Notch1/2 and DLL4 after Mycobacterium tuberculosis infection, may play a role in childhood tuberculosis by acting on other target genes, and further studies are needed for clarification.