血清核苷酸结合寡聚化结构域样受体蛋白3对脓毒症诊断及预后的价值

Value of serum nucleotide-bound oligomerized domain-like receptor protein 3 in the diagnosis and prognosis of sepsis

目的 探讨血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)对脓毒症诊断及预后的评估价值。方法 前瞻性纳入脓毒症患者100例作为脓毒症组,选择同期64例我院健康体检者作为对照组。根据sepsis3.0诊断标准将所有脓毒症患者分为脓毒症亚组(66例)和脓毒性休克组(34例),根据28 d生存情况将所有脓毒症患者再分为存活组(76例)和死亡组(24例)。收集所有受试者的一般临床资料及血清NLRP3水平,收集脓毒症患者入ICU后24 h内和对照组实验室检查结果及脓毒症患者入ICU后24 h内C反应蛋白(CRP)、序贯器官衰竭(SOFA)评分、急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分和其感染部位。采用Pearson相关分析评估NLRP3与临床指标的相关性。采用受试者工作特征(ROC)曲线分析NLRP3对脓毒症诊断及预后的评估价值。采用Cox回归分析评估影响脓毒症患者预后的危险因素。结果 脓毒症组患者年龄、血乳酸(Lac)、降钙素原(PCT)、总胆红素、AST、血肌酐(SCr)、IL-6及血清NLRP3水平均高于对照组(P<0.05)。脓毒性休克组患者年龄、总胆红素、IL-6、血清NLRP3水平及APACHEⅡ评分、SOFA评分均明显高于脓毒症亚组,血Lac水平低于脓毒症亚组(P<0.05)。Pearson相关分析结果显示,脓毒症患者血清NLRP3水平与血Lac、IL-6、APACHEⅡ评分和SOFA评分均呈正相关(P<0.05)。ROC曲线分析结果显示,血清NLRP3诊断脓毒症的ROC曲线下面积(AUC)为0.893,血清NLRP3诊断脓毒性休克的AUC为0.750。单因素Cox回归分析结果显示,年龄、血SCr、血Lac、IL-6、血清NLRP3、APACHEⅡ评分均是影响脓毒症患者预后的影响因素;多因素Cox回归分析结果显示,IL-6及APACHEⅡ评分均是影响脓毒症患者预后的独立危险因素(P<0.05)。死亡组患者血清NLRP3水平明显高于存活组(P<0.05)。血清NLRP3和IL-6对脓毒症患者预后诊断价值的AUC均高于APACHEⅡ评分。结论 血清NLRP3水平与脓毒症患者疾病严重程度及炎症反应相关,对脓毒症有较好的诊断和预后评估价值,具有作为脓毒症生物标志物的潜力。

Objective To evaluate the value of serum nucleotide-bound oligomerized domain-like receptor protein 3(NLRP3) in the diagnosis and prognosis of sepsis.Methods A tatal of 100 patients with sepsis were prospectively included as sepsis group,and 64 healthy subjects from our hospital in the same period were selected as control group.According to sepsis 3.0 diagnostic criteria,all sepsis patients were divided into sepsis subgroup(66 cases) and septic shock group(34 cases),and all sepsis patients were further divided into survival group(76 cases) and death group(24 cases) according to 28 d survival.General clinical data and serum NLRP3 level were collected for all subjects.Laboratory test results of sepsis patients within 24 h after admission to ICU and control group were collected,C-reactive protein(CRP),sequential organ failure(SOFA) score,Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ) score and infection site of sepsis patients within 24 h after admission to ICU were collected.Pearson correlation analysis was used to evaluate the correlation between NLRP3 and clinical indicators.The value of NLRP3 in the diagnosis and prognosis of sepsis was analyzed by receiver operating characteristic(ROC) curve.Cox regression was used to analyze the risk factors affecting the prognosis of sepsis patients.Results Age,blood lactate(Lac),procalcitonin(PCT),total bilirubin,AST,serum creatinine(SCr),IL-6 and serum NLRP3 levels in sepsis group were higher than those in control group(P<0.05).Age,total bilirubin,IL-6,serum NLRP3 level,APACHEⅡ score and SOFA score in septic shock group were significantly higher than those in sepsis subgroup,and blood Lac level was lower than that in sepsis subgroup(P<0.05).Pearson correlation analysis results showed that serum NLRP3 level was positively correlated with Lac,IL-6,APACHEⅡ score and SOFA score in sepsis patients(P<0.05).ROC curve analysis results chowed that the area under ROC curve(AUC) of serum NLRP3 for the diagnosis of sepsis was 0.893 and the AUC of serum NLRP3 for the diagnosis of septic shock was 0.750.Univariate Cox regression analysis showed that age,blood SCr,blood Lac,IL-6,serum NLRP3,APACHEⅡ scores were all factors affecting the prognosis of sepsis patients;Multivariate Cox regression analysis showed that IL-6 and APACHEⅡ scores were independent risk factors for the prognosis of sepsis patients(P<0.05).The serum NLRP3 level in death group was significantly higher than that in survival group(P<0.05).The AUC of serum NLRP3 and IL-6 for the prognostic value of sepsis patients was higher than that of APACHEⅡ score.Conclusion Serum NLRP3 level is correlated with disease severity and inflammatory response in sepsis patients,which has a good diagnostic and prognostic value for sepsis,and has potential as a biomarker of sepsis.