轮状病毒感染性腹泻患儿外周血STING、TBK1基因表达及肠道微环境变化

Expressions of STING, TBK1 genes in peripheral blood and change of intestinal microenvironment in children with rotavirus infectious diarrhea

目的 探究轮状病毒感染性腹泻(RVID)患儿外周血干扰素基因刺激蛋白(STING)、TANK连接激酶1(TBK1)基因表达情况,分析RVID患儿肠道微环境及免疫功能。方法 选取2018年6月-2021年6月湖南省人民医院收治的RVID患儿117例为RVID组,同期于本院接受体检的健康儿童105名为对照组,采用实时荧光定量PCR法检测外周血STING、TBK1基因表达情况;采用16S rRNA基因扩增和高通量测序对肠道菌群结构进行分析;比较两组血清1,25-二羟维生素D3[1,25-(OH)2VitD3]和免疫指标水平。结果 RVID组STING、TBK1 mRNA表达水平低于对照组(P<0.05);肠道菌群α多样性分析结果显示,RVID组Chao1指数和辛普森指数低于对照组(P<0.05);RVID组门水平上厚壁菌门、拟杆菌门相对丰度高于对照组(P<0.05),RVID组属水平上双歧杆菌属、拟杆菌属和乳酸杆菌属相对丰度低于对照组(P<0.05);RVID组血清1,25-(OH)2VitD3和IgA、IgG、IgM表达水平均低于对照组(P<0.05)。结论 STING、TBK1基因在RVID患儿外周血中呈低表达水平,RVID患儿与健康儿童的肠道微环境存在差异,肠道菌群紊乱可能会加剧RVID患儿机体免疫功能失调。

OBJECTIVE To explore the expressions of stimulator of interferon genes(STING) and TANK-binding kinase 1(TBK1) genes in peripheral blood of children with rotavirus infectious diarrhea(RVID) and observe the intestinal microenvironment and immune function of the children with RVID. METHODS A total of 117 children with RVID who were treated in Hunan Provincial People′s Hospital from Jun 2018 to Jun 2021 were assigned as the RVID group, meanwhile, 105 healthy children who received physical examination were chosen as the control group. The expression levels of peripheral blood STING and TBK1 genes were detected by real-time fluorescent quantitative PCR, the structure of intestinal flora was analyzed by 16S rRNA gene amplification and high-throughput sequencing. The levels of serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2VitD3] and immune indexes were observed and compared between the two groups of patients. RESULTS The expression levels of STING and TBK1 mRNA of the RVID group were lower than those of the control group(P<0.05). The intestinal flora alpha diversity analysis showed that Chao 1 index and Simpson index of the RVID group were lower than those of the control group(P<0.05);as compared with the phylum, the relative abundance of Firmicutes and Bacteroides of the RVID group was higher than that of the control group;as compared with the genus, the relative abundance of Bifidobacterium, Bacteroides and Lactobacillus of the RVID group was lower than that of the control group(P<0.05). The expression levels of serum 1,25-(OH)2VitD3, IgA, IgG and IgM of the RVID group were lower than those of the control group(P<0.05). CONCLUSION The children with RVID show low expression levels of peripheral blood STING and TBK1 genes, the children with RVID and the healthy children vary in intestinal microenvironment, and the disturbance of intestinal flora may aggravate the immune dysfunction of the children with RVID.