2025 年第 7 期 第 20 卷

癫痫持续状态患儿血清微小RNA-330-5p和Toll样受体4的表达与神经炎症反应及预后的关系

The relationship between the expression of serum microRNA-330-5p and Toll-like receptor 4 and neuroinflammatory response and prognosis in children with status epilepticus

作者：金欣1张晓栋2吴松3

英文作者：Jin Xin1 Zhang Xiaodong2 Wu Song3

单位：1三二〇一医院儿科，汉中723000；2陕西省汉中市人民医院儿科，汉中723000；3三二〇一医院检验科，汉中723000

英文单位：1Department of Pediatrics 3201 Hospital Hanzhong 723000 China; 2Department of Pediatrics Hanzhong People′s Hospital Shaanxi Province Hanzhong 723000 China; 3Department of Clinical Laboratory 3201 Hospital Hanzhong 723000 China

关键词：癫痫持续状态；微小RNA-330-5p；Toll样受体4；神经炎症反应；预后

英文关键词：Statusepilepticus;MicroRNA-330-5p;Toll-likereceptor4;Neuroinflammatoryresponse;Prognosis

• 摘要：

• 目的 探讨癫痫持续状态（SE）患儿血清微小RNA(miR)-330-5p、Toll样受体4（TLR4）的表达与神经炎症反应及预后的关系。方法 选取2021年1月至2023年11月三二〇一医院收治的98例SE患儿为SE组，根据入院后28 d预后分为预后不良组（37例）和预后良好组（61例），另选取同期40名健康儿童为对照组，检测血清miR-330-5p、TLR4和神经炎症反应因子［白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）］表达。通过在线网站预测miR-330-5p与TLR4的结合位点，Pearson相关系数分析SE患儿血清miR-330-5p与TLR4表达的相关性；以SE患儿预后为因变量，多因素Logistic回归分析确定影响因素，受试者工作特征曲线分析血清miR-330-5p、TLR4表达对患儿预后不良的预测价值。结果 与对照组比较，SE组血清miR-330-5p表达降低，TLR4、IL-1β、IL-6、TNF-α表达升高（均P＜0.001）。miR-330-5p与TLR4 3′-非翻译区5310-5317处存在结合位点，SE患儿血清miR-330-5p与TLR4、IL-1β、IL-6、TNF-α表达均呈负相关（r=-0.686、-0.672、-0.646、-0.687，均P＜0.001），TLR4与IL-1β、IL-6、TNF-α表达呈正相关（r=0.711、0.679、0.701，均P＜0.001）。SE发作时间≥1 h（比值比=4.317，95%置信区间：1.011～18.435）、儿童癫痫持续状态严重程度评分增加（比值比=2.749，95%置信区间：1.392～5.428）和IL-1β升高（比值比=1.067，95%置信区间：1.010～1.127）、IL-6升高（比值比=1.137，95%置信区间：1.014～1.275）、TNF-α升高（比值比=1.343，95%置信区间：1.051～1.716）、TLR4升高（比值比=2.375，95%置信区间：1.133～4.978）为SE患儿预后不良的独立危险因素，miR-330-5p升高（比值比=0.933，95%置信区间：0.888～0.980）为独立保护因素（均P＜0.05）。血清miR-330-5p、TLR4表达单独与二者联合对SE患儿预后不良的预测曲线下面积（AUC）依次为0.794（95%置信区间：0.700～0.869）、0.797（95%置信区间：0.703～0.871）、0.881（95%置信区间：0.800～0.938），二项联合预测AUC最大（均P＜0.05）。结论 SE患儿血清miR-330-5p低表达和TLR4高表达与神经炎症反应增强、预后不良密切相关，血清miR-330-5p、TLR4表达联合对SE患儿预后不良具有较高的预测价值。

• Objective  To investigate the relationship between the expression of serum microRNA (miR)-330-5p and Toll-like receptor 4 (TLR4) and neuroinflammatory response and prognosis in children with status epilepticus (SE). Methods A total of 98 children with SE admitted to 3201 Hospital from January 2021 to November 2023 were selected as the SE group. According to the prognosis 28 days after admission, they were divided into poor prognosis group (37 cases) and good prognosis group (61 cases), and 40 healthy children in the same period were selected as the control group. The levels of serum miR-330-5p, TLR4 and neuroinflammatory markers ［interleukin 1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α)］ were detected. The binding sites of miR-330-5p and TLR4 were predicted by online websites. The correlation between serum miR-330-5p and TLR4 was analyzed by Pearson correlation coefficient. The prognosis of children with SE was used as the dependent variable, and multivariate Logistic regression analysis was used to determine the influencing factors. The receiver operating characteristic curve was used to analyze the predictive value of serum miR-330-5p and TLR4 in the poor prognosis of children with SE. Results Compared with the control group, the expression of serum miR-330-5p in the SE group was decreased, and the expressions of TLR4, IL-1β, IL-6 and TNF-α were increased (all P<0.001). There was a binding site between miR-330-5p and TLR4 3 ′-untranslated region 5310-5317. The expression of serum miR-330-5p was negatively correlated with the expression of TLR4, IL-1β, IL-6, TNF-α in children with SE (r=-0.686, -0.672, -0.646, -0.687, all P＜0.001), the expression of TLR4 was positively correlated with the expression of IL-1β, IL-6 and TNF-α (r=0.711, 0.679, 0.701, all P<0.001). The onset time of SE ≥1 h［odds ratio(OR)=4.317, 95% confidence interval (CI): 1.011 to 18.435］, the increased severity score of SE(OR=2.749, 95%CI: 1.392 to 5.428), and the increased levels of IL-1β(OR=1.067, 95%CI: 1.010 to 1.127), IL-6(OR=1.137, 95%CI: 1.014 to 1.275), TNF-α(OR=1.343, 95%CI: 1.051 to 1.716) and TLR4(OR=2.375, 95%CI: 1.133 to 4.978) were independent risk factors for poor prognosis of SE children, and the increased level of miR-330-5p was an independent protective factor(OR=0.933, 95%CI: 0.888 to 0.980)(all P＜0.05). The area under the curve (AUC) of serum miR-330-5p and TLR4 expression alone and in combination for predicting poor prognosis in children with SE were 0.794 (95%CI: 0.700 to 0.869), 0.797 (95%CI: 0.703 to 0.871), and 0.881 (95%CI: 0.800 to 0.938) in order, and the binomial joint prediction AUC was the largest (both P<0.05). Conclusion Low expression of serum miR-330-5p and high expression of TLR4 are closely related to increased neuroinflammation and poor prognosis in children with SE. The combination of serum miR-330-5p and TLR4 has a high predictive value for poor prognosis in children with SE.