川崎病合并支原体感染病儿瓣膜炎性损伤与IL-6/STAT3信号通路表达变化的关系分析

Relationship between valvular inflammatory injury and changes of IL-6/STAT3 signaling pathways in children with Kawasaki disease and mycoplasma infection

目的探讨川崎病(KD)合并支原体感染病儿瓣膜炎性损伤与白细胞介素-6(IL-6)/信号转导及转录激活蛋白3(STAT3)信号通路表达变化的关系。方法前瞻性选取2018年1月至2022年12月安阳市妇幼保健院收治的50例KD合并肺炎支原体(MP)(KD-MP)感染病儿为感染组,另选取同期收治的106例单纯KD病儿为未感染组,比较感染组与未感染组病儿瓣膜炎性损伤情况。再根据KD病儿是否伴有冠状动脉损伤(CAL)损伤分为CAL组(n=84)、无CAL组(n=72),比较两组病儿IL-6和STAT3表达水平,通过多因素logistic回归分析KD病儿发生CAL的危险因素。比较KD并CAL不同预后病儿IL-6和STAT3表达变化,使用受试者操作特征曲线(ROC曲线)分析IL-6、STAT3水平对KD并CAL病儿预后的预测价值。结果感染组KD病儿发热时间、住院时间、初诊CAL发生率均高于未感染组(P<0.05);感染组KD病儿C反应蛋白(CRP)、降钙素原(PCT)、红细胞沉降率(ESR)、IL-6 mRNA表达水平和STAT3 mRNA表达水平均高于未感染组[(51.32±12.62)mg/L比(36.58±10.98)mg/L,(1.33±0.35)μg/L比(1.21±0.31)μg/L,(84.69±15.66)mm/h比(49.62±16.43)mm/h,4.14±1.09比3.06±1.15,2.81±0.89比1.68±0.54,均P<0.05]。CAL组病儿IL-6、STAT3 mRNA表达水平高于无CAL组(4.13±1.22比2.56±0.87,2.46±0.71比1.55±0.44,均P<0.05);多因素回归分析结果显示,MP感染、IL-6 mRNA、STAT3 mRNA表达是KD病儿发生CAL的独立危险因素(均P<0.05)。KD并CAL预后良好组病儿IL-6、STAT3 mRNA表达水平低于预后不良组(3.57±1.06比4.57±1.13,1.94±0.58比2.87±0.87,均P<0.05),ROC曲线结果显示IL-6、STAT3及其联合预测KD并CAL预后的曲线下面积(AUC)分别为0.75、0.81、0.91,且联合检测的AUC高于IL-6、STAT3单独检测(均P<0.05)。结论KD合并MP病儿瓣膜炎性损伤更为严重,IL-6/STAT3信号通路活化是其危险因素,且该信号通路对KD并CAL病儿预后有较高的预测价值。

Objective To explore the relationship between valvular inflammatory injury and changes of interleukin-6(IL-6)/signal transducer and activator of transcription protein 3(STAT3)signaling pathways in children with Kawasaki disease(KD)and mycoplasma infection.Methods A total of 50 children with KD and Mycoplasma pneumoniae(KD-MP)infection in Anyang Maternal and Child Health Hospital between January 2018 and December 2022 were prospectively enrolled as infection group,while other 106 children only with KD during the same period were enrolled as non-infection group.The valvular inflammatory injury in the two groups was compared.According to presence or absence of coronary artery lesion(CAL),children with KD were divided into CAL group(n=84)and non-CAL group(n=72),and expression levels of IL-6 and STAT3 were compared between the two groups.The risk factors of CAL in KD children were analyzed by multivariate logistic regression analysis.The changes of IL-6 and STAT3 in children with different prognosis were compared.The predictive value of IL-6 and STAT3 for prognosis of children with KD and CAL was analyzed by receiver operating characteristic curves(ROC curves).Results The fever time,hospitalization time and incidence of newly diagnosed CAL in infection group were higher than those in non-infection group(P<0.05).The levels of C-reactive protein(CRP),procalcitonin(PCT),erythrocyte sedimentation rate(ESR),IL-6 mRNA and STAT3 mRNA in infection group were higher than those in non-infection group[(51.32±12.62)mg/L vs.(36.58±10.98)mg/L,(1.33±0.35)μg/L vs.(1.21±0.31)μg/L,(84.69±15.66)mm/h vs.(49.62±16.43)mm/h,4.14±1.09 vs.3.06±1.15,2.81±0.89 vs.1.68±0.54,P<0.05].The expression levels of IL-6 and STAT3 mRNA in CAL group were higher than those in non-CAL group(4.13±1.22 vs.2.56±0.87,2.46±0.71 vs.1.55±0.44,P<0.05).The results of multivariate regression analysis showed that MP infection,IL-6 and STAT3 were independent risk factors of CAL in KD children(P<0.05).The expression levels of IL-6 and STAT3 mRNA in good prognosis group were lower than those in poor prognosis group(3.57±1.06 vs.4.57±1.13,1.94±0.58 vs.2.87±0.87,P<0.05).The results of ROC curves analysis showed that area under curve(AUC)values of IL-6,STAT3 and combined detection for predicting the prognosis were 0.75,0.81 and 0.91,respectively.AUC of combined detection was greater than that of single index(P<0.05).Conclusions The valvular inflammatory injury is severer in children with KD and MP.The activated IL-6/STAT3 signaling pathways are risk factors for valvular inflammatory injury,which have high prognostic value in children with KD and CAL.