手足口病患儿血清LTB4和COX2水平表达与疾病严重程度及预后的相关性研究

Correlation between Serum LTB4 and COX-2 Levels Expression and Disease Severity,Prognosis in Children with Hand-Foot-and-Mouth Disease

目的 探讨手足口病(hand-foot-and-mouth disease,HFMD)患儿血清白三烯B4(leukotriene B4,LTB4)、环氧合酶-2(cyclooxygenase-2,COX-2)水平与疾病严重程度及预后的相关性。方法 选取盘锦辽油宝石花医院感染科收治的HFMD患儿120例(HFMD组)作为研究对象,根据疾病严重程度分为普通组48例、重型组43例和危重型组29例,根据患儿28天预后结局分为预后良好组(n=104)与预后不良组(n=16);另选取同期体检的健康幼儿120例为对照组。酶联免疫吸附(enzyme-linked immunosorbent assay,ELISA)法测定血清LTB4,COX-2,白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平,Pearson法分析血清LTB4,COX-2水平与血清IL-6,TNF-α水平的相关性,受试者工作特征(receiver operating characteristic,ROC)曲线评估血清LTB4和COX-2水平对HFMD患儿预后的预测价值。结果 与对照组相比,HFMD组血清LTB4(43.86±12.35ng/L vs 24.03±6.05 ng/L),COX-2(43.39±12.74μg/L vs 22.15±5.41μg/L),IL-6(48.56±12.83ng/L vs 13.88±3.27ng/L)和TNF-α(273.83±40.56 ng/L vs 37.49±6.79 ng/L)水平均升高,差异具有统计学意义(t=15.796~62.955,均P<0.05);与普通组相比,重型组、危重型组患儿血清LTB4(49.63±8.74 ng/L,64.05±9.68 ng/L vs 29.57±6.53ng/L),COX-2(52.83±9.48μg/L,60.45±10.16μg/L vs 27.32±6.73μg/L),IL-6(59.30±9.43ng/L,78.75±10.36ng/L vs 21.88±6.14 ng/L),TNF-α(342.47±23.69 ng/L,448.92±38.76 ng/L vs 106.55±16.24 ng/L)水平均升高,差异具有统计学意义(t=16.509~79.715,均P<0.05);与重型组相比,危重型组患儿血清LTB4,COX-2,IL-6和TNF-α水平均升高,差异具有统计学意义(t=5.173~24.260,均P<0.05);HFMD患儿血清LTB4,COX-2水平与IL-6,TNF-α水平均呈正相关(r=0.548,0.598;0.534,0.718,均P<0.05);与预后良好组相比,预后不良组HFMD患儿血清LTB4(60.27±13.71ng/L vs 41.34±8.54ng/L),COX-2(56.48±9.28μg/L vs 41.38±12.33μg/L)水平均升高,差异有统计学意义(t=7.534,4.691,均P<0.05)。血清LTB4和COX-2表达水平预测HFMD患儿预后不良的ROC曲线下面积分别为0.883,0.832,截断值分别为53.98 ng/L,48.33μg/L,敏感度分别为68.8%,87.5%,特异度分别为93.3%,68.3%,两者联合预测的ROC曲线下面积、敏感度和特异度分别为0.936,81.3%和95.2%。结论 HFMD患儿血清LTB4和COX-2水平升高,与疾病严重程度及炎症因子水平均密切相关,具有一定预后评估价值。

Objective To investigate the correlation between serum leukotriene B4(LTB4),cyclooxygenase-2(COX-2)levels and the severity,prognosis of hand-foot-and-mouth disease(HFMD).Methods A total of 120 children with HFMD(HFMD group)in the Infection Department of Panjin Liaoyou Gem Flower Hospital were selected as the research objects.According to the severity of the disease,they were divided into normal group(n=48),severe group(n=43)and critical group(n=29).According to the 28-day prognosis,they were divided into good prognosis group(n=104)and poor prognosis group(n=16).Another 120healthy children in the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to determine the levels of LTB4,COX-2,IL-6 and TNF-αin serum,Pearson method was used to analyze the correlation between serum LTB4,COX-2 levels and serum IL-6,TNF-αlevels,receiver operating characteristic(ROC)curve was used to evaluate the prognostic value of serum LTB4 and COX-2 levels in children with HFMD.Results Compared with those in the control group,the serum levels of LTB4(43.86±12.35ng/L vs 24.03±6.05ng/L),COX-2(43.39±12.74μg/L vs 22.15±5.41μg/L),IL-6(48.56±12.83ng/L vs 13.88±3.27ng/L)and TNF-α(273.83±40.56 ng/L vs 37.49±6.79 ng/L)were increased in HFMD group and the differences were statistically significant(t=15.796~62.955,all P<0.05).Compared with those in the normal group,the serum levels of LTB4(49.63±8.74 ng/L,64.05±9.68 ng/L vs 29.57±6.53ng/L),COX-2(52.83±9.48μg/L,60.45±10.16μg/L vs 27.32±6.73μg/L),IL-6(59.30±9.43ng/L,78.75±10.36ng/L vs 21.88±6.14 ng/L)and TNF-α(342.47±23.69 ng/L,448.92±38.76 ng/L vs 106.55±16.24 ng/L)were increased in severe group and critical group,the differences were statistically significant(t=16.509~79.715,all P<0.05).Compared with those in the severe group,the serum levels of LTB4,COX-2,IL-6 and TNF-αwere increased in the critical group and the differences were statistically significant(t=5.173~24.260,all P<0.05).The serum levels of LTB4,COX-2 were positively correlated with IL-6 and TNF-αin the HFMD group(r=0.548,0.598;0.534,0.718,all P<0.05).Compared with those in the good prognosis group,the serum levels of LTB4(60.27±13.71ng/L vs 41.34±8.54ng/L)and COX-2(56.48±9.28μg/L vs 41.38±12.33μg/L)were increased in the poor prognosis group and the differences were statistically significant(t=7.534,4.691,all P<0.05).The area under ROC curve of serum LTB4 and COX-2 expression levels for predicting poor prognosis of HFMD children was 0.883 and 0.832,respectively,and the cut-off value was 53.98 ng/L and 48.33μg/L,respectively.The sensitivity was 68.8%and 87.5%,and the specificity was 93.3%and 68.3%,respectively,and the combined predicted the area under ROC curve,sensitivity and specificity under the ROC curves were 0.936,81.3%and 95.2%,respectively.Conclusion The serum levels of LTB4 and COX-2 in children with HFMD were increased,which were closely related to the severity of the disease and the level of inflammatory factors,and have certain prognostic value.