蛛网膜下腔出血患者TLR4/NF-κB信号通路变化及意义

Changes and Significance of TLR4/NF-κB Signaling Pathway in Patients with Subarachnoid Hemorrhage

目的探究蛛网膜下腔出血患者Toll样受体4(Toll like receptor 4,TLR4)/核因子κB(nuclear factor kappa B,NF-κB)信号通路变化及意义。方法选取作者医院2018-05/2021-06月收治的60例蛛网膜下腔出血患者作为观察组,另选取同期体检健康者60例作为对照组。比较两组TLR4/NF-κB信号通路相关因子表达,分析蛛网膜下腔出血患者TLR4/NF-κB信号通路相关因子与神经功能损害美国国立卫生院卒中量表(national institutes of health stroke scale,NIHSS)评分的关系。比较不同预后患者发病第1、3、7、14天外周血TLR4/NF-κB信号通路相关因子,绘制受试者工作特征(receiver operating characteristic,ROC)曲线,评价TLR4/NF-κB信号通路相关因子对蛛网膜下腔出血患者预后的预测价值,分析TLR4/NF-κB信号通路相关因子与蛛网膜下腔出血患者预后不良风险的关系。结果观察组TLR4 mRNA、NF-κB mRNA表达均高于对照组,组间比较差异有统计学意义(P均<0.05)。蛛网膜下腔出血患者入院当天NIHSS评分为(11.24±3.12)分,根据Pearson相关性模型分析可知,蛛网膜下腔出血患者TLR4 mRNA、NF-κB mRNA表达均与NIHSS评分呈正相关关系(P<0.05)。不同组别间患者TLR4 mRNA、NF-κB mRNA相对表达量差异有统计学意义(F组间=8.037、19.348,P均<0.001),不同时间点患者TLR4 mRNA相对表达量差异有统计学意义(F时间=5.128、16.207,P均<0.001),且时间与组间存在交互效应(F交互=6.497、18.032,P=0.015、<0.001)。预后不良组患者发病第1天TLR4 mRNA、NF-κB mRNA相对表达量较预后良好组患者差异无统计学意义(P>0.05)。预后不良组患者发病第3天、7天、14天TLR4 mRNA、NF-κB mRNA相对表达量均高于预后良好组患者(P均<0.05)。预后不良组患者、预后良好组患者发病第3天TLR4 mRNA、NF-κB mRNA相对表达量升至最高(P均<0.05);发病第7天、14天TLR4 mRNA、NF-κB mRNA相对表达量均较发病第3天明显下降,且发病第14天降至最低(P均<0.05)。以预后不良作为阳性样本,预后良好作为阴性样本,绘制ROC曲线,结果显示,发病第3、7、14天TLR4 mRNA、NF-κB mRNA联合预测蛛网膜下腔出血患者预后的AUC分别为0.854、0.894、0.915,较各指标单独诊断价值明显提高。Logistic回归分析显示,TLR4 mRNA、NF-κB mRNA仍与蛛网膜下腔出血患者预后不良有关(P均<0.05)。结论蛛网膜下腔出血后TLR4/NF-κB信号通路被激活,TLR4 mRNA、NF-κB mRNA表达明显上调,且TLR4/NF-κB信号通路与蛛网膜下腔出血患者早期脑损伤有关,为临床治疗提供了新思路,有助于改善患者预后。

Objective To investigate the changes and significance of Toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway in patients with subarachnoid hemorrhage.Methods A total of 60 patients with subarachnoid hemorrhage who were treated in author′s hospital from May 2018 to June 2021 were selected as the observation group,and 60 healthy people who underwent physical examination during the same period were selected as the control group.The expression of TLR4/NF-κB signaling pathway related factors between the two groups was compared,and the relationship between TLR4/NF-κB signaling pathway related factors and national institutes of health stroke scale(NIHSS)scores in patients with subarachnoid hemorrhage was analyzed.Factors related to TLR4/NF-κB signaling pathway in peripheral blood of patients with different prognosis at the 1st,3rd,7th and 14th days were compared;receiver operating characteristic(ROC)curve was drawn;the predictive value of TLR4/NF-κB signaling pathway related factors on the prognosis of patients with subarachnoid hemorrhage were evaluated,and the relationship between factors related to TLR4/NF-κB signaling pathway and the risk of poor prognosis in patients with subarachnoid hemorrhage were analyzed.Results The expressions of TLR4 mRNA and NF-κB mRNA in the observation group was higher than those in the control group,and the difference was statistically significant(all P<0.05).The NIHSS score of patients with subarachnoid hemorrhage was(11.24±3.12)on the day of admission,and the expression of TLR4 mRNA and NF-κB mRNA in patients with subarachnoid hemorrhage were positively correlated with the NIHSS score according to the Pearson correlation model(P<0.05).There were statistically significant differences in the relative expression levels of TLR4 mRNA and NF-κB mRNA among different groups(Finterblock=8.037,19.348,all P<0.001),the relative expression level of TLR4 mRNA in patients at different timing had statistical significance(Ftime=5.128,16.207,all P<0.001),and there was an interaction effects between time and groups(Finteraction=6.497,18.032,P=0.015,<0.001).There was no significant difference in the relative expression levels of TLR4 mRNA and NF-κB mRNA in patients with poor prognosis compared with those with good prognosis on the first day of the outset(P>0.05).The relative expression levels of TLR4 mRNA and NF-κB mRNA in patients with poor prognosis were higher than those in patients with good prognosis at the 3rd,7th and 14th days(all P<0.05).The relative expression levels of TLR4 mRNA and NF-κB mRNA in patients with poor prognosis and good prognosis increased to the highest level on the 3rd day of the outset(all P<0.05).The relative expression levels of TLR4 mRNA and NF-κB mRNA on the 7th and 14th days of the outset significantly decreased compared with the 3rd day of the outset,and decreased to the lowest level on the 14th day of the outset(all P<0.05).ROC curve was drawn with poor prognosis as positive samples and good prognosis as negative samples.The results showed that the AUC of TLR4 mRNA and NF-κB mRNA combined to predict the prognosis of patients with subarachnoid hemorrhage were 0.854,0.894 and 0.915 on the 3rd,7th and 14th days of the outset respectively,which was significantly higher than the diagnostic value of each indicator alone.Logistic regression analysis showed that TLR4 mRNA and NF-κB mRNA were still associated with poor prognosis in patients with subarachnoid hemorrhage(all P<0.05).Conclusion TLR4/NF-κB signaling pathway is activated after subarachnoid hemorrhage,the expressions of TLR4 mRNA and NF-κB mRNA are significantly up-regulated,and TLR4/NF-κB signaling pathway is related to early brain injury in patients with subarachnoid hemorrhage,which provides a new idea for clinical treatment and helps to improve the prognosis of patients.