血清ATX、Angptl4、S100 A12与脓毒症并发ARDS患者NLRP3炎性小体及预后的关系

Correlations of serum autotaxin,angiopoietin like protein 4,S100 calcium-binding protein A12 and NLRP3 inflammatory bodies with prognosis in patients with sepsis complicated with acute respiratory distress syndrome

目的 探讨血清自分泌运动因子(autotaxin, ATX)、血管生成素样蛋白4(angiopoietin-like protein 4,Angptl4)、S100钙结合蛋白A12(S100 calcium-binding protein A12,S100A12)与脓毒症并发急性呼吸窘迫综合征(ARDS)患者NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor pyrin domain containing 3,NLRP3)炎性小体以及预后的关系。方法 选取2019年1月至2022年4月收治的303例脓毒症患者,根据是否合并ARDS分为ARDS组(106例)和非ARDS组(197例),比较两组研究对象的血清ATX、Angptl4、S100A12、NLRP3及细胞因子白细胞介素(IL)-1β及IL-18水平,采用Pearson相关系数法分析血清ATX、Angptl4、S100A12水平与NLRP3、IL-1β及IL-18水平的相关性。根据ARDS组患者住院期间预后情况分为生存组(57例)与死亡组(49例),分析两组患者临床资料,并采用logistic回归分析模型分析导致脓毒症并发ARDS患者住院期间死亡的危险因素;绘制受试者工作特征(ROC)曲线,分析血清ATX、Angptl4、S100A12单独及联合检测对脓毒症并发ARDS患者住院期间死亡的预测价值。结果 ARDS组血清ATX、Angptl4、S100A12、NLRP3、IL-1β及IL-18水平均高于非ARDS组(P<0.05)。Pearson分析显示,血清ATX、Angptl4、S100A12与NLRP3 mRNA、IL-1β、IL-18水平均呈正相关(P<0.05)。死亡组年龄、急性生理与慢性健康评分Ⅱ(APACHEⅡ)、序贯器官衰竭评估(SOFA)评分、血乳酸、血清ATX、Angptl4、S100A12水平以及休克、机械通气时间≥3 d、ICU入住时间≥10 d、侵入性置管患者的占比均高于生存组,氧合指数(OI)、白蛋白水平低于生存组(P<0.05)。多因素logistic回归分析显示,入院时APACHEⅡ、SOFA评分、血清ATX、Angptl4、S100A12升高均是导致患者死亡的危险因素(P<0.05)。ROC曲线分析显示,血清ATX、Angptl4、S100A12及三者联合预测脓毒症并发ARDS患者住院期间死亡的曲线下面积(AUC)分别为0.729、0.708、0.780、0.852,三血清指标联合预测效能高于单项检测。结论 脓毒症并发ARDS患者血清ATX、Angptl4、S100A12水平升高,与NLRP3炎性小体及其细胞因子关系密切,且是影响住院期间病情转归的独立危险因素,联合检测血清ATX、Angptl4、S100A12有助于脓毒症并发ARDS患者短期预后的判断。

Objective To investigate the correlations of serum autotaxin(ATX),angiopoietin-like protein 4(Angptl4),S100 calcium-binding protein A12(S100A12)and NOD-like receptor pyrin domain containing 3(NLRP3)inflammasome with the prognosis in patients with sepsis complicated with acute respiratory distress syndrome(ARDS).Methods From January 2019 to April 2022,303 patients with sepsis were selected,and were divided into ARDS group(106 cases)and non-ARDS group(197 cases)according to whether they had ARDS or not.The serum ATX,Angptl4,S100A12,NLRP3 and the cytokines interleukin(IL)-1βand IL-18 levels were compared between the two groups.The correlations of serum ATX,Angptl4,S100A12 levels with NLRP3,IL-1βand IL-18 levels were analyzed by Pearson correlation coefficient.According to the prognosis of patients in the ARDS group during hospitalization,they were divided into survival group(57 cases)and death group(49 cases).The clinical data of the two groups were analyzed,and the risk factors of patients with sepsis complicated with ARDS during hospitalization were analyzed by logistic regression analysis model.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum ATX,Angptl4 and S100A12 alone and in combination for in-hospital death of patients with sepsis complicated with ARDS.Results Serum ATX,Angptl4,S100A12,NLRP3,IL-1βand IL-18 levels in the ARDS group were significantly higher than those in the non-ARDS group(P<0.05).Pearson analysis showed that serum ATX,Angptl4 and S100A12 were positively correlated with NLRP3 mRNA,IL-1βand IL-18 levels(P<0.05).The proportion of age,acute physiological and chronic health scoreⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)score,blood lactic acid,serum ATX,Angptl4,S100A12 levels,shock,mechanical ventilation time≥3 d,ICU stay time≥10 d,invasive catheterization of patients in the death group were significantly higher than those in the survival group;while the oxygenation index(OI)and albumin level were significantly lower than those in the survival group(P<0.05).Multivariate logistic regression analysis showed that the elevated of APACHEⅡon admission,SOFA score,serum ATX,Angptl4 and S100A12 were all risk factors for death(P<0.05).ROC curve analysis showed that the areas under curve(AUC)of ATX,Angptl4,S100A12 and their combination in predicting the in-hospital death of patients with sepsis complicated with ARDS were 0.729,0.708,0.780 and 0.852,respectively;the combined predictive efficacy of the three serum indexes was higher than that of the single detection.Conclusion The serum levels of ATX,Angptl4 and S100A12 in patients with sepsis complicated with ARDS are increased,which are closely related to NLRP3 inflammasome and its cytokines,and are independent risk factors affecting the outcome of the disease during hospitalization.Combined detection of serum ATX,Angptl4 and S100A12 is helpful to the short-term prognosis of patients with sepsis complicated with ARDS.