重症急性胰腺炎患者外周血TLR4、TRAF6的表达及与并发肝损伤的关系

Expressions of TLR4 and TRAF6 in the peripheral blood of patients with severe acute pancreatitis and their associations with liver injury

摘要:

目的 探讨Toll样受体4（TLR4）、肿瘤坏死因子受体相关因子6（TRAF6）水平在重症急性胰腺炎（SAP）外周血中的表达及与并发肝损伤的关系。方法 选取2018年10月—2021年10月厦门长庚医院收治的187例SAP患者，依据是否发生肝损伤分为肝损伤组和无肝损伤组。对比肝损伤组和无肝损伤组临床资料、TLR4和TRAF6 mRNA相对表达量。采用多因素Logistic逐步回归模型分析SAP患者发生肝损伤的相关因素。绘制受试者工作特征（ROC）曲线，分析外周血TLR4 mRNA、TRAF6 mRNA及两者联合检测对SAP患者肝损伤发生的预测价值。结果 187例SAP患者并发肝损伤62例，未并发肝损伤125例。肝损伤组急性胰腺炎床旁严重度指数（BISAP）评分、脂肪酶、淀粉酶（AMY）、白细胞介素-6（IL-6）、C反应蛋白（CRP）、降钙素原（PCT）、肿瘤坏死因子-α（TNF-α）、TLR4 mRNA、TRAF6 mRNA相对表达量高于无肝损伤组（P <0.05）。多因素Logistic逐步回归分析结果显示：BISAP评分［O^R=2.892（95% CI：1.482，5.645）］、TLR4 mRNA ［O^R=3.334（95% CI：1.710，6.512）］、TRAF6 mRNA ［O^R=3.059（95% CI：1.567，5.970）］均为影响SAP患者肝损伤发生的危险因素（P <0.05）。ROC曲线分析结果显示，外周血TLR4 mRNA、TRAF6 mRNA及两者联合预测SAP患者肝损伤发生的敏感性分别为80.65%（95% CI：0.621，0.872）、77.42%（95% CI：0.546，0.824）、75.81%（95% CI：0.534，0.819），特异性分别为73.60%（95% CI：0.503，0.796）、80.80%（95% CI：0.617，0.863）、99.20%（95% CI：0.725，0.998），曲线下面积分别为0.792（95% CI：0.727，0.848）、0.824（95% CI：0.762，0.876）、0.856（95% CI：0.797，0.903）。结论 外周血TLR4、TRAF6表达均与SAP患者并发肝损伤有关，且外周血TLR4 mRNA、TRAF6 mRNA联合检测对SAP患者发生肝损伤的预测效能较高。

Abstract:

Objective To investigate the expressions of Toll-like receptor 4 (TLR4) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in peripheral blood of patients with severe acute pancreatitis (SAP) and their associations with liver injury.Methods A total of 187 patients with SAP admitted to our hospital from October 2018 to October 2021 were selected and divided into the occurrence group and the non-occurrence group based on the presence of liver injury. The clinical data and the mRNA expressions of TLR4 and TRAF6 of patients in the occurrence group and the non-occurrence group were compared. The multivariable Logistic regression analysis was performed to determine the factors affecting the occurrence of liver injury in SAP patients. The receiver operating characteristic (ROC) curve was plotted to analyze the predictive values of the levels of TLR4 and TRAF6 in peripheral blood alone and their combination for the occurrence of liver injury in SAP patients.Results Among 187 SAP patients, 62 cases were complicated with liver injury, while the rest 125 patients were not complicated with liver injury. The Bedside Index for Severity in Acute Pancreatitis (BISAP) score, the levels of lipase, amylase (AMY), interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and tumor necrosis factor (TNF), and the mRNA expressions of TLR4 and TRAF6 in the occurrence group were higher than those in the non-occurrence group (P < 0.05). The multivariable Logistic regression analysis showed that the BISAP score [O^R =2.892 (95% CI: 1.482, 5.645) ], and the mRNA expressions of TLR4 [O^R = 3.334 (95% CI: 1.710, 6.512) ] and TRAF6 [O^R = 3.059 (95% CI: 1.567, 5.970) ] were factors affecting the occurrence of liver injury in SAP patients (P < 0.05). The ROC curve analysis revealed that the sensitivities of the mRNA expressions of TLR4 and TRAF6 in peripheral blood alone and their combination in predicting liver injury in SAP patients were 80.65% (95% CI: 0.621, 0.872), 77.42% (95% CI: 0.546, 0.824), and 75.81% (95% CI: 0.534, 0.819), with the corresponding specificities being 73.60% (95% CI: 0.503, 0.796), 80.80% (95% CI: 0.617, 0.863), and 99.20% (95% CI: 0.725, 0.998), and the corresponding areas under the ROC curves (AUCs) being 0.792 (95% CI: 0.727, 0.848), 0.824 (95% CI: 0.762, 0.876) and 0.856 (95% CI: 0.797, 0.903), respectively.Conclusions The expressions of TLR4 and TRAF6 in peripheral blood are related to liver injury in SAP patients, and the combination of the mRNA expressions of TLR4 and TRAF6 in peripheral blood exhibits a high predictive value for the occurrence of liver injury in SAP patients.