血清Nrf2和TIMP3水平在川崎病早期诊断及预后中的意义

The Significance of Serum Nrf2 and TIMP3 Levels in the Early Diagnosis and Prognosis of Kawasaki Disease

目的探讨血清核因子红细胞2相关因子(Nrf2)和组织抑制剂金属蛋白酶3(TIMP3)表达在川崎病(KD)早期诊断及预后中的意义。方法选取2019年9月至2021年9月我院收治的KD患儿84例为研究对象(KD组),另选取同期我院体检中心进行体检的健康儿童84例作为对照组,其中KD组根据患儿预后情况又分为冠状动脉病变(CAL)组(18例)及无CAL组(66例),收集基本资料及实验室指标。酶联免疫吸附法(ELISA)检测血清Nrf2和TIMP3水平;相关性分析采用Pearson法;绘制受试者工作特征(ROC)曲线分析血清Nrf2和TIMP3水平预测KD及CAL的价值。结果KD组血清Nrf2和TIMP3水平显著低于对照组,血小板计数(PLT)、白细胞介素-6(IL-6)、血沉(ESR)及氨基末端脑钠肽前体(NT-proBNP)水平均显著高于对照组(P<0.05);KD患儿血清Nrf2与IL-6、NT-proBNP均呈负相关(r=-0.512、-0.530,P<0.05),血清TIMP3与IL-6、NT-proBNP均呈负相关(r=-0.465、-0.482,P<0.05);ROC曲线显示,Nrf2诊断KD的AUC为0.769,截断值为789.85 U/L,其敏感度、特异度分别为79.76%、67.86%,TIMP3诊断KD的AUC为0.790,截断值为147.76 pg/ml,其敏感度、特异度分别为65.48%、79.76%,二者联合诊断KD的AUC为0.857,明显高于二者单独诊断(Z_(联合vs.Nrf2)=2.951、P=0.003,Z_(联合vs.TIMP3)=2.658、P=0.008)。CAL组血清Nrf2和TIMP3显著低于无CAL组,IL-6、ESR及NT-proBNP水平均显著高于无CAL组(P<0.05);ROC曲线显示,Nrf2预测CAL的AUC为0.812,截断值为634.12 U/L,其敏感度、特异度分别为94.44%、62.12%,TIMP3预测CAL的AUC为0.736,截断值为127.71 pg/ml,其敏感度、特异度分别为94.44%、48.48%,二者联合预测CAL的AUC为0.889,明显高于二者单独预测(Z_(联合vs.Nrf2)=2.254、P=0.024,Z_(联合vs.TIMP3)=2.724、P=0.006)。结论KD患儿血清Nrf2、TIMP3低表达,二者联合用于KD诊断及预后均有一定价值。

Objective To investigate the significance of the expression levels of serum nuclear factor erythrocyte 2 related factor(Nrf2)and tissue inhibitor metalloproteinase 3(TIMP3)in the early diagnosis and prognosis of Kawasaki disease(KD).Methods From September 2019 to September 2021,84 children with KD admitted to our hospital were selected as the study object,and were set as KD group,in addition,84 healthy children who were examined in the physical examination center of our hospital at the same time were selected as the control group.KD group was divided into coronary artery disease(CAL)group(18 cases)and non CAL group(66 cases)according to the prognosis of children,basic data and laboratory indicators were collected.Serum Nrf2 and TIMP3 levels were detected by enzyme-linked immunosorbent assay(ELISA);Pearson method was used for correlation analysis;and ROC curve was drawn to analyze the value of serum Nrf2 and TIMP3 levels in predicting KD and CAL.Results The levels of Nrf2 and TIMP3 in KD group were obviously lower than those in control group,and the levels of platelet count(PLT),interleukin-6(IL-6),erythrocyte sedimentation rate(ESR)and N-terminal pro brain natriuretic peptide(NT-proBNP)were obviously higher than those in control group(P<0.05);serum Nrf2 was negatively correlated with IL-6 and NT-proBNP in KD children(r=-0.512,-0.530,P<0.05),and serum TIMP3 was negatively correlated with IL-6 and NT-proBNP(r=-0.465,-0.482,P<0.05);ROC curve showed that the AUC of KD diagnosed by Nrf2 was 0.769,the cut-off value was 789.85 U/L,the sensitivity and specificity were 79.76%and 67.86%,respectively,and the AUC of KD diagnosed by TIMP3 was 0.790,the cut-off value was 147.76 pg/ml,the sensitivity and specificity were 65.48%and 79.76%,respectively.The AUC of KD diagnosed by the combination of the two methods was 0.857,which was obviously higher than that diagnosed by the two methods alone(Z_(combination vs.Nrf2)=2.951,P=0.003,Z_(combination vs.TIMP3)=2.658,P=0.008).Serum Nrf2 and TIMP3 levels in CAL group were obviously lower than those in non CAL group,and IL-6,ESR and NT-proBNP levels were obviously higher than those in non CAL group(P<0.05);ROC curve showed that the AUC of CAL predicted by Nrf2 was 0.812,the cut-off value was 634.12 U/L,the sensitivity and specificity were 94.44%and 62.12%respectively,and the AUC of CAL predicted by TIMP3 was 0.736,the cut-off value was 127.71 pg/ml,the sensitivity and specificity were 94.44%and 48.48%respectively,the AUC of CAL predicted by the combination of the two methods was 0.889,which was obviously higher than that predicted by the two methods alone(Z_(combination vs.Nrf2)=2.254,P=0.024,Z_(combination vs.TIMP3)=2.724,P=0.006).Conclusion The expression of Nrf2 and TIMP3 in KD children is low,both of them are valuable in the diagnosis and prognosis of KD.