儿童感染性腹泻病原学及外周血单个核细胞STING和TBKI与ISG15表达水平

Etiological characteristics and STING,TBK1 and ISG15 expression in peripheral blood mononuclear cells of children with infectious diarrhea

目的 探讨感染性腹泻患儿病原菌及外周血单个核细胞(PBMC)干扰素基因刺激蛋白(STING)、TANK结合激酶1(TBK1)和外周血干扰素刺激基因15(ISG15)的表达意义。方法 选取2018年4月-2020年12月百色市妇幼保健院收治的感染性腹泻患儿104例设为研究组,另选同期健康儿童90名作为对照组,统计感染性腹泻患儿临床特征,收集患儿粪便样本进行病原微生物鉴定和耐药性分析;抽取所有入组儿童外周血,检测PBMC中STING、TBK1和ISG15基因的mRNA表达水平,受试者工作特征(ROC)曲线分析PBMC中STING、TBK1和ISG15表达水平对感染性腹泻的诊断效能。结果 感染性腹泻患儿临床表现多为腹泻及排便异常,53.85%患儿伴有腹胀腹痛,43.27%患儿以稀水便为主,41.35%患者伴有发热症状;革兰阴性菌和病毒是感染性腹泻的主要病原体。革兰阴性菌共51株占49.04%,以志贺菌属和沙门菌属为主;病毒共43株,占41.35%,以轮状病毒和诺如病毒为主;研究组患儿PBMC中STING、TBK1和ISG15的相对mRNA水平高于对照组(P<0.05);与病毒感染组相比,细菌感染组患儿PBMC中STING、TBK1和ISG15的相对mRNA水平更高(P<0.05);当STING>1.43、TBK1>1.29、TBK1>1.47时诊断感染性腹泻效能最佳(P<0.05),当PBMC中STING>1.88、TBK1>1.65、ISG15>1.91时诊断感染源效能最佳(P<0.05)。结论 感染性腹泻患儿的主要致病微生物为细菌和病毒,患儿PBMC中STING、TBK1和ISG15基因表达水平显著升高,并在细菌性感染中水平更高,其表达水平的变化与感染性腹泻的发病以及感染来源有关。

OBJECTIVE To investigate the pathogenic bacteria and expressions of stimulator of interferon genes(STING),TANK binding kinase 1(TBK1) and interfero stimulated gene 15(ISG15) in peripheral blood mononuclear cells(PBMC) in children with infectious diarrhea.METHODS Totally 104 children with infectious diarrhea treated in the Baise Maternal and Child Health Care Hospital between Apr.2018 and Dec.2020 were selected as the study group,and 90 healthy children during the same period were selected as the control group.The clinical characteristics of children with infectious diarrhea were statistically analyzed,and the stool samples of children were collected for pathogenic microorganism identification and drug resistance analysis.The peripheral blood of all enrolled children was extracted to detect the mRNA expression levels of STING,TBK1 and ISG15 genes in PBMC,and receiver operating characteristic(ROC) curve was used to analyze the diagnostic efficiency of expression levels of STING,TBK1 and ISG15 in PBMC for infectious diarrhea.RESULTS The clinical manifestations of children with infectious diarrhea were mostly diarrhea and abnormal defecation,including 53.85% of children with abdominal distension and abdominal pain,43.27% of children with watery stools and 41.35% of children with fever.Gram-negative bacteria and viruses were the main pathogens of infectious diarrhea.A total of 51 strains of Gram-negative bacteria accounted for 49.04%,mainly Shigella and Salmonella;43 strains of viruses accounted for 41.35%,mainly Rotavirus and Norovirus.The relative mRNA levels of STING,TBK1 and ISG15 in PBMC in study group were higher than those in control group(P<0.05).The relative mRNA levels of STING,TBK1 and ISG15 were higher in PBMC of children in the bacterial infection group compared to the viral infection group(P<0.05).When STING was higher than 1.43,TBK1 was higher than 1.29 and ISG15 was higher than 1.47,the diagnostic efficiency of infectious diarrhea was the best(P<0.05).When STING was higher than 1.88,TBK1 was higher than 1.65 and ISG15 was higher than1.91 in PBMC,the efficiency was the best in diagnosing infection source(P<0.05).CONCLUSION The main pathogenic microorganisms in children with infectious diarrhea were bacteria and viruses,and the expression levels of STING,TBK1 and ISG15 genes in PBMC of children were significantly increased,especially in children with bacteria infections,which were associated with the onset of infectious diarrhea and the source of infection.