大承气汤辅助治疗成人急性呼吸窘迫综合征对患者血清ANGPTL4表达及临床预后的影响

Effect of Dachengqi Decoction on serum ANGPTL4 expression and clinical prognosis in assisted treatment of patients with adult acute respiratory distress syndrome

目的探讨成人急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)患者血清血管生成素样4(angiopoietin like 4,ANGPTL4)水平与患者病情分级的关系,大承气汤辅助西医治疗对患者血清ANGPTL4水平的影响,以及与患者临床预后的关系,寻找敏感性和特异性更佳的生化指标。方法回顾性研究2019年8月—2021年8月新乡市中心医院确诊的ARDS患者122例,根据入院氧合指数(PaO_(2)/FiO_(2))分为轻度44例、中度48例和重度30例,同期选择年龄和性别相匹配的健康受试者40例作为对照组。ARDS患者采用大承气汤辅助西医治疗5 d。比较对照组和ARDS不同分级患者间治疗前临床资料,比较治疗28 d临床预后ARDS存活与死亡患者间临床资料及治疗前后血清ANGPTL4、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和动脉血乳酸水平变化。多因素COX回归分析筛选28 d死亡的独立危险因素;Kaplan-Meier法绘制不同ANGPTL4表达组患者的生存曲线;受试者工作曲线(receiver operating characteristic,ROC)计算28 d死亡的曲线下面积(area under curve,AUC)。结果对照组和轻度、中度与重度ARDS患者的入院急性生理学及慢性健康状况Ⅱ(acute physiology and chronic health scoreⅡ,APACHEⅡ)评分、序贯器官衰竭评估(sequential organ failure assessment,SOFA)评分,血清ANGPTL4、IL-6和TNF-α水平比较,差异均有统计学意义(P<0.05),呈逐渐升高趋势。治疗28 d后存活82例和死亡40例,死亡患者入院APACHEⅡ和SOFA评分、血清ANGPTL4水平明显高于存活患者,而PaO_(2)/FiO_(2)水平明显低于存活患者(P<0.05);存活患者治疗后血清ANGPTL4水平较治疗前低,比死亡患者明显降低,差异有统计学意义(P<0.05)。多因素Cox回归分析显示,入院APACHEⅡ评分、SOFA评分、PaO_(2)/FiO_(2)和ANGPTL4水平是成人ARDS死亡的独立危险因素(P<0.05)。Kaplan-Meier曲线显示,ANGPTL4低表达患者28 d累积生存率明显高于ANGPTL4高表达患者(P<0.05)。ROC结果显示,入院APACHEⅡ评分、SOFA评分、PaO_(2)/FiO_(2)和ANGPTL4预测死亡的AUC分别为0.803、0.724、0.844和0.897,ANGPTL4的AUC值明显高于APACHEⅡ评分和SOFA评分(P<0.05),与PaO_(2)/FiO_(2)比较差异无统计学意义(P>0.05)。结论成人ARDS患者入院血清ANGPTL4水平升高与疾病发生、严重程度以及临床预后密切相关,大承气汤辅助西医治疗能够明显降低ANGPTL4水平,ANGPTL4有望成为ARDS诊断和预后评估的新型生化标志物。

Objective To investigate the relationship between admission serum angiopoietin like 4(ANGPTL4)level and disease severity in adult patients with acute respiratory distress syndrome(ARDS),the influence of Dachengqi Decoction(大承气汤)assisted western medicine treatment on serum ANGPTL4 level of patients and the relationship with clinical prognosis of patients,so as to find biochemical index with better sensitivity and specificity.Methods A retrospective study of 122 ARDS patients diagnosed in Xinxiang Central Hospital from August 2019 to August 2021 was divided into 44 mild cases,48 moderate cases and 30 severe cases according to admission oxygen index(PaO2/FiO2).Forty age-and sex-matched healthy subjects were selected as the control group.ARDS patients were treated with Dachengqi Decoction assisted western medicine treatment for 5 d.The clinical data before treatment between the control group and patients with different grades of ARDS were compared,and the clinical data of ARDS survival and death patients at 28 d after treatment,and the changes of serum ANGPTL4,interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and arterial blood lactate levels before and after treatment were compared.Multivariate COX regression analysis was used to screen independent risk factors for 28-d death;Kaplan-Meier method was used to draw survival curves of patients with different ANGPTL4 expression groups;Receiver operating characteristic(ROC)was used to calculate the area under the curve(AUC)of 28-d death.Results Admission acute physiology and chronic healthⅡ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,serum ANGPTL4,IL-6 and TNF-αlevels in control group,mild group,moderate group and severe group were significant differences(P<0.05),they all showed a gradual upward trend.The ANGPTL4 level after treatment in survival patients were lower than before treatment,and was significantly less than death patients(P<0.05).Admission APACHEⅡscore,SOFA score and serum ANGPTL4 level in death group were significantly higher than survival group,while PaO2/FiO2 level was lower(P<0.05).Multivariate Cox regression analysis showed that admission APACHEⅡscore,SOFA score,PaO2/FiO2 and ANGPTL4 level were the independent risk factors of death(P<0.05).Kaplan-Meier curve showed that 28 d cumulative survival rate of ANGPTL4 low-expression group was significantly higher than ANGPTL4 high-expression group(P<0.05).ROC showed that the AUC of admission APACHEⅡscore,SOFA score,PaO2/FiO2 and ANGPTL4 for predicting death were 0.803,0.724,0.844 and 0.897,respectively,AUC of ANGPTL4 was significantly higher than APACHEⅡscore and SOFA score(P<0.05),while no difference compared to PaO2/FiO2(P>0.05).Conclusion Higher serum ANGPTL4 admission level in adult patients with ARDS is closely related to the occurrence,severity and survival prognosis.Dachengqi Decoction assisted western medicine treatment could greatly reduce ANGPTL4 level.ANGPTL4 is expected to become a new biomarker for the diagnosis and prognosis of ARDS.