HMGB1和vWF等细胞因子对脓毒症患者病情严重程度及预后评估的意义

Significance of high mobility group box 1,von Willebrand factor and other cytokines in the evaluation of severity and prognosis of sepsis patients

目的探讨高迁移率族蛋白B1(HMGB1)、血管性血友病因子(vWF)等细胞因子对脓毒症患者病情严重程度及预后的预测价值.方法以2019年1月至6月入住滨州医学院附属医院重症医学科年龄≥18岁且符合Sepsis-3诊断标准的脓毒症及脓毒性休克患者作为研究对象;以同期健康体检者作为对照.记录患者的基本信息及急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)和序贯器官衰竭评分(SOFA);于确诊后24 h内取静脉血,采用酶联免疫吸附试验(ELISA)测定血清HMGB1、vWF、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、可溶性血栓调节蛋白(sTM)、血管内皮生长因子受体2(VEGFR-2)、血管生成素-2(Ang-2)等细胞因子水平.比较脓毒症患者、脓毒性休克患者、健康体检者,以及28 d死亡患者与存活患者各指标的差异;采用Spearman等级相关法分析各细胞因子与APACHEⅡ和SOFA评分的相关性;绘制受试者工作特征曲线(ROC),评估细胞因子对脓毒症/脓毒性休克患者预后的预测价值;用Logistic回归分析患者28 d死亡的危险因素.结果入选脓毒症患者11例,脓毒性休克患者25例,健康体检者30例;脓毒症/脓毒性休克患者中28 d死亡15例,存活21例.脓毒症患者血清TNF-α、IL-10、HMGB1、vWF、sTM、VEGFR-2均较健康对照组明显升高;脓毒性休克组TNF-α、IL-10、HMGB1、vWF、sTM较脓毒症组进一步升高,而Ang-2水平则显著下降.脓毒症/脓毒性休克死亡者TNF-α、IL-10、HMGB1、vWF、sTM均明显高于存活者,而Ang-2低于存活者.Spearman相关分析显示,脓毒症/脓毒性休克患者入组时HMGB1、TNF-α、sTM、IL-10、vWF均与APACHEⅡ评分呈正相关(r值分别为0.652、0.666、0.445、0.430、0.355,均P<0.05),且HMGB1、TNF-α与SOFA评分也呈正相关(r值分别为0.433、0.479,均P<0.05);而Ang-2与APACHEⅡ和SOFA评分均呈负相关(r值分别为-0.519、-0.440,均P<0.05).ROC曲线分析显示,HMGB1、vWF、IL-10、sTM对脓毒症/脓毒性休克患者28 d死亡的预测价值均高于APACHEⅡ评分〔ROC曲线下面积(AUC)和95%可信区间(95%CI):0.946(0.870~1.000)、0.902(0.790~1.000)、0.877(0.745~1.000)、0.868(0.734~1.000)比0.846(0.700~0.991)〕.Logistic回归分析显示,APACHEⅡ评分、vWF、sTM、IL-10是脓毒症/脓毒性休克患者28 d死亡的独立危险因素(β值分别为4.731、0.407、-7.058、-0.887,均P<0.05).结论HMGB1、vWF、IL-10、sTM等细胞因子均可判断脓毒症患者病情严重程度及预后.

Objective To explore the value of high mobility group box 1(HMGB1),von Willebrand factor(vWF)and other cytokines in predicting the severity and prognosis of sepsis patients.Methods Patients with sepsis and septic shock who≥18 years old and met the Sepsis-3 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to June 2019 were taken as the research objects.The healthy individuals for regular health examination in the same period were taken as the control.The basic information,acute physiology and chronic health evaluationⅡ(APACHEⅡ)and sequential organ failure assessment(SOFA)scores were recorded.The venous blood was taken within 24 hours after the patients were diagnosed.The levels of HMGB1,vWF,tumour necrosis factor-α(TNF-α),interleukin-10(IL-10),soluble thrombomodulin(sTM),vascular endothelial growth factor receptor 2(VEGFR-2),angiopoetin-2(Ang-2)and other cytokines in serum were determined by enzyme linked immunosorbent assay(ELISA).Differences among patients with sepsis,septic shock,healthy physical examinees,and patients who died in 28-day and those who survived,were compared.Spearman rank correlation method was used to analyze the correlation among each cytokine and APACHEⅡ,SOFA scores.The receiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of cytokines on the prognosis of patients with sepsis/septic shock.Logistic regression was used to analyze the risk factors of 28-day death.Results Eleven patients with sepsis,25 patients with septic shock and 30 healthy individuals were enrolled.Among the patients with sepsis/septic shock,15 died in 28-day and 21 survived.The serum levels of TNF-α,IL-10,HMGB1,vWF,sTM and VEGFR-2 in patients with sepsis were significantly higher than those in the healthy control group.The levels of TNF-α,IL-10,HMGB1,vWF,sTM in septic shock group were higher than those in the sepsis group,while the Ang-2 level decreased significantly.The serum levels of TNF-α,IL-10,HMGB1,vWF and sTM in the death group were higher than those in the survival group,while Ang-2 was lower than the survival group.Spearman correlation analysis showed that HMGB1,TNF-α,sTM,IL-10,vWF were positively correlated with APACHEⅡscore when patients with sepsis/septic shock were enrolled(r values were 0.652,0.666,0.445,0.430 and 0.355,respectively,all P<0.05),and HMGB1,TNF-αalso positively correlated with SOFA score(r values were 0.433,0.479,both P<0.05).Ang-2 was negatively correlated with APACHEⅡand SOFA scores(r values were-0.519,-0.440,both P<0.05).ROC curve analysis showed that the predictive value of HMGB1,vWF,IL-10,sTM for 28-day death in patients with sepsis/septic shock were higher than the APACHEⅡscore[the area under ROC curve(AUC)and 95%confidence interval(95%CI):0.946(0.870-1.000),0.902(0.790-1.000),0.877(0.745-1.000),0.868(0.734-1.000)vs.0.846(0.700-0.991)].Logistic regression analysis showed that APACHEⅡscore,vWF,sTM,and IL-10 were independent risk factors for 28-day death in patients with sepsis/septic shock(βvalues were 4.731,0.407,-7.058,-0.887,all P<0.05).Conclusion HMGB1,vWF,IL-10,sTM and other cytokines all can be used to evaluate the severity and prognosis of sepsis patients.