重症急性胰腺炎cf-DNA/NETs、sTREM-1及GP-2α水平与病情关系

Correlations of serum cf-DNA/NETs,sTREM-1 and GP-2αlevels with the severity of acute pancreatitis

目的探讨重症急性胰腺炎(severe acute pancreatitis,SAP)患者血清游离DNA/中性粒细胞胞外诱捕网(cell-free DNA/nertrophil extracellular traps,cf-DNA/NETs)、可溶性髓系细胞触发受体-1(soluble triggering receptor expresses on myeloid cell-1,sTREM-1)、糖蛋白-2α(glycoprotein-2,GP-2α)水平变化,分析cf-DNA/NETs、sTREM-1、GP-2α与SAP病情进展的关系。方法105例胰腺炎患者,其中58例SAP患者为SAP组,47例单纯急性胰腺炎患者为胰腺炎组,根据28 d生存情况将SAP组分为生存组46例和死亡组12例。采用ELISA法检测血清sTREM-1和GP-2α水平,采用PicoGreen荧光染料定量分析检测cf-DNA/NETs表达水平;绘制ROC曲线,评估cf-DNA/NETs、sTREM-1、GP-2α单独和联合检测预测SAP病情严重程度的效能;采用多因素logistic回归分析影响SAP患者预后的因素。结果SAP组患者入院第1天血清cf-DNA/NETs[(1175.53±274.26)μg/L]、sTREM-1[(91.66±20.49)ng/L]、GP-2α[(5.09±1.82)u]水平均高于胰腺炎组[(623.17±178.35)μg/L、(63.25±15.92)ng/L、(3.53±1.26)u](P<0.05);入院第1、3、7天,死亡组血清cf-DNA/NETs、sTREM-1、GP-2α水平均高于生存组(P<0.05);当cf-DNA/NETs、sTREM-1、GP-2α最佳截断值分别为1262.15μg/L、98.19 ng/L、6.88 u时,预测SAP病情严重程度的AUC分别为0.824(95%CI:0.706~0.943,P=0.001)、0.857(95%CI:0.705~1.000,P<0.001)、0.689(95%CI:0.506~0.873,P=0.045),灵敏度分别为75.00%、91.7%、60.00%,特异度分别为80.4%、80.4%、93.4%,三者联合预测SAP病情严重程度的AUC为0.940,敏感度为91.7%、特异度为82.6%;cf-DNA/NETs(OR=2.37,95%CI:1.45~3.89,P=0.006)、sTREM-1(OR=2.32,95%CI:1.24~4.36,P=0.004)和GP-2α(OR=3.19,95%CI:1.72~5.91,P<0.001)是SAP患者预后的影响因素。结论SAP患者血清cf-DNA/NETs、sTREM-1、GP-2α呈高表达,且随病情加重而升高,均是影响SAP患者预后的危险因素,可用于评估SAP病情严重程度。

Objective To investigate the changes of cell-free DNA/neutrophil extracellular traps(cf-DNA/NETs),soluble triggering receptor expresses on myeloid cell-1(sTREM-1)and glycoprotein-2α(GP-2α)levels in patients with severe acute pancreatitis(SAP),and to analyze their relationships with the progression of SAP.Methods Totally 105 patients with pancreatitis were divided into SAP group(n=58)and acute pancreatitis(AP)group(n=47),and were divided into survival group(n=46)and death group(n=12)according to the 28-day survival.The levels of sTREM-1 and GP-2α were detected by ELISA,and the level of cf-DNA/NETs was detected by PicoGreen fluorescent dye quantitative analysis.ROC was drawn to evaluate the efficacies of single and joint detection of cf-DNA/NETs,sTREM-1 and GP-2α on predicting the severity of SAP.Multivariate logistic regression analysis was used to analyze the influencing factors for the prognosis of SAP.Results The levels of cf-DNA/NETs,sTREM-1 and GP-2αwere significantly higher in SAP group((1175.53±274.26)μg/L,(91.66±20.49)ng/L,(5.09±1.82)u)than those in AP group((623.17±178.35)μg/L,(63.25±15.92)ng/L,(3.53±1.26)u)on the 1 st day of admission(P<0.05),and were higher on the 1st,3rd and 7th day of admission in death group than those in survival group(P<0.05).When the optimal cut-off values of cf-DNA/NETs,sTREM-1 and GP-2αwere 1262.15μg/L,98.19 ng/L and 6.88 u,the AUCs for predicting the severity of SAP were 0.824(95%CI:0.706-0.943,P=0.001),0.857(95%CI:0.705-1.000,P<0.001)and 0.689(95%CI:0.506-0.873,P=0.045),with the sensitivities of 75.00%,91.7% and 60.00%,and the specificities of 80.4%,80.4% and 93.4%,respectively.The AUCof joint detection of them three for predicting the severity of SAP was 0.940,with a sensitivity of 91.7%,and a specificity of 82.6%.cf-DNA/NETs(OR=2.37,95%CI:1.45-3.89,P=0.006),sTREM-1(OR=2.32,95%CI:1.24-4.36,P=0.004)and GP-2α(OR=3.19,95%CI:1.72-5.91,P<0.001)were the influencing factors for the prognosis of SAP.Conclusion The levels of serum cf-DNA/NETs,sTREM-1 and GP-2αin SAP patients are highly expressed and keep rising as the patients get worse,and all are the influencing factors for the prognosis of SAP,therefore they can be used to evaluate the severity of SAP.