TLR4、NF-κB在溃疡性结肠炎儿童血清中的表达及与预后复发的关系

Expression of TLR4 and NF-κB in serum of children with ulcerative colitis and their relationships with recurrence in prognosis

摘要

目的 探究Toll样受体4(TLR4)、核转录因子-κB(NF-κB)在溃疡性结肠炎(UC)儿童血清中的表达及与预后复发的关系。方法 选取湖州市第一人民医院儿科2021年11月至2023年11月期间收治的80例UC患儿为UC组,并依据病情严重程度分为轻度组(n=30)、中度组(n=28)与重度组(n=22),另选取同期30例体检健康儿童为健康组。比较四组儿童外周血TLR4 mRNA、NF-κB mRNA表达水平,采用Spearman法分析外周血TLR4、NF-κB与UC病情严重程度的相关性。另根据患儿随访6个月的复发情况,将UC组分为复发组(n=21)与未复发组(n=59)。采用多因素Logistic分析UC预后复发的影响因素,受试者工作特征(ROC)曲线分析TLR4、NF-κB对UC预后复发的预测效能。结果 外周血TLR4 mRNA、NF-κB mRNA表达水平比较,重度组>中度组>轻度组>健康组(均P<0.05);Spearman相关分析显示,UC患儿病情严重程度与外周血TLR4 mRNA、NF-κB mRNA表达水平呈正相关(r=0.533、0.617,P<0.05);Logistic回归分析显示,病情严重程度为重度、病变范围为全结肠型(E4)、出院后未接受维持治疗、外周血TLR4 mRNA、NF-κB mRNA表达水平升高为UC预后复发的独立危险因素(OR介于1.793到2.243之间,均P<0.05);ROC曲线显示,外周血TLR4、NF-κB以及二者联合预测UC预后复发的曲线下面积(AUC)分别为0.783、0.789以及0.863,且二者联合的预测价值最佳。结论 外周血TLR4 mRNA、NF-κB mRNA表达上调是溃疡性结肠炎患儿预后复发的独立危险因素,且二者联合对溃疡性结肠炎患儿预后复发的预测效能较高。

Abstract

Objective To investigate expression of toll-like receptor 4 (TLR4) and nuclear transcription factor-κB (NF-κB) in serum of children with ulcerative colitis (UC) and their relationships with recurrence in prognosis. Methods A total of 80 children with UC who were treated in Department of Pediatrics,The First Huzhou Municipal People's Hospital over a period from November 2021 to November 2023 were selected in UC group,and according to disease severity,these children were further divided into three subgroups:mild UC subgroup (n=30),moderate UC subgroup (n=28) and severe UC subgroup (n=22).Other 30 healthy children who received physical examination in the same period were selected as healthy control group.The expression levels of TLR4 mRNA and NF-κB mRNA in peripheral blood of the children were compared among the four groups.Spearman correlation analysis was used to analyze correlations of TLR4 and NF-κB in peripheral blood with severity of UC.In addition,according to whether the UC recurred at follow-up after 6 months,the children in the UC group were divided into recurrence group (n=21) and non-recurrence group (n=59).Multivariate Logistic analysis was used to analyze influencing factors of UC recurrence in prognosis.Receiver operating characteristic (ROC) curve was used to analyze predictive efficacy of TLR4 and NF-κB for UC recurrence in prognosis. Results The expression levels of TLR4 mRNA and NF-κB mRNA in peripheral blood in the severe UC subgroup > those in the moderate UC subgroup > those in the mild UC subgroup > those in the healthy control group (all P<0.05).Spearman correlation analysis showed that the severity of UC disease was positively correlated with expression levels of TLR4 mRNA and NF-κB mRNA in peripheral blood (r=0.533 and 0.617 respectively,both P<0.05).Multivariate regression analysis showed that severe disease severity,total colonic type of UC (E4) in lesion range,no maintenance treatment after discharge,and elevated levels of TLR4 mRNA and NF-κB mRNA in peripheral blood were all independent risk factors for UC recurrence in prognosis (OR=1.793-2.243,all P<0.05).ROC curve analysis showed that the areas under the curve (AUCs) of TLR4 mRNA and NF-κB mRNA in peripheral blood and the combination of the two indexes for predicting UC recurrence in prognosis were 0.783,0.789 and 0.863 respectively,suggesting that the combined detection of the two indexes had the best predictive efficacy (P<0.05). Conclusion The up-regulated expressions of TLR4 mRNA and NF-κB mRNA in peripheral blood are two independent risk factor for UC recurrence in prognosis,and the combined detection of TLR4 mRNA and NF-κB mRNA is more effective in predicting UC recurrence in prognosis in children.

关键词

儿童 / 溃疡性结肠炎 / Toll样受体4 / 核转录因子-κB / 预后复发

Key words

children / ulcerative colitis / toll-like receptor 4 / nuclear transcription factor-κB / recurrence in prognosis

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基金资助

湖州市科学技术计划项目(2023GYB39)