2024 年第 4 期 第 19 卷

中性粒细胞胞外诱捕网在肝衰竭患者中的促炎作用研究

Study on the pro-inflammatory effects of neutrophil extracellular traps in patients with liver failure

作者：杨世欣石春霞郭金张丹眉张清奇龚作炯

英文作者：Yang Shixin Shi Chunxia Guo Jin Zhang Danmei Zhang Qingqi Gong Zuojiong

单位：武汉大学人民医院感染科，武汉430060

英文单位：Department of Infectious Diseases Renmin Hospital of Wuhan University Wuhan 430060 China

关键词：肝衰竭；中性粒细胞胞外诱捕网；髓过氧化物酶；炎症

英文关键词：国家自然科学基金（82270627）

• 摘要：

• 目的 探讨中性粒细胞胞外诱捕网(NETs)在肝衰竭患者中的促炎作用和NETosis在肝衰竭肝脏炎症反应过程中的致病作用。方法 选取2020年10月至2022年2月于武汉大学人民医院就诊的30例肝衰竭患者作为观察组，选取同期体检健康人群30例作为对照组。比较2组受试者的血清生化指标，采用酶联免疫吸附试验法检测血清中NETs标志物髓过氧化物酶(MPO)-DNA水平，采用免疫荧光法检测中性粒细胞中NETs标志物分子MPO和中性粒细胞弹性蛋白酶(NE)水平，采用免疫组织化学染色法检测供肝和肝衰竭患者肝组织中MPO水平。结果 观察组凝血酶原活动度、白蛋白水平均低于对照组，观察组中性粒细胞百分比、总胆红素、丙氨酸转氨酶、天冬氨酸转氨酶水平均高于对照组（均P＜0.05）。酶联免疫吸附试验结果显示观察组MPO-DNA水平高于对照组［（10.0±2.7）μg/L比（3.4±1.0）μg/L］(P＜0.001)。免疫荧光结果显示观察组外周血中性粒细胞中NE、MPO表达水平均高于对照组。免疫组织化学染色结果显示肝衰竭患者肝组织中MPO的表达水平高于供肝组织。结论 肝衰竭时，中性粒细胞活化产生NETs，并通过NETosis促进肝脏炎症反应，加重肝脏损伤。

• Objective To investigate the pro-inflammatory effect of neutrophil extracellular traps (NETs) in patients with liver failure and the pathogenic role of NETosis in the process of liver inflammation in liver failure. Methods A total of 30 patients with liver failure treated in Renmin Hospital of Wuhan University from October 2020 to February 2022 were selected as the observation group, and 30 healthy people in the same period were selected as the control group. The serum biochemical indexes of the two groups were compared. The concentration of myeloperoxidase (MPO)-DNA in serum was detected by enzyme-linked immunosorbent assay （ELISA）, and the levels of MPO and neutrophil elastase (NE) in neutrophils were detected by immunofluorescence method. MPO levels in donor livers and liver failure patients were detected by immunohistochemical staining. Results The prothrombin activity and albumin level in the observation group were lower than those in the control group, and the percentage of neutrophils, and the levels of total bilirubin, alanine aminotransferase and aspartate aminotransferase in the observation group were higher than those in the control group (all P＜0.05). The results of ELISA showed that the level of MPO-DNA in the observation group was higher than that in the control group ［(10.0±2.7)μg/L vs (3.4±1.0)μg/L］(P＜0.001). Immunofluorescence results showed that the expression levels of NE and MPO in peripheral blood neutrophils in the observation group were higher than those in the control group. The results of immunohistochemical staining showed that the expression level of MPO in liver tissues of liver failure patients was higher than that in donor liver tissues. Conclusion In liver failure, neutrophils are activated to produce NETs, which promote liver inflammation through NETosis and aggravate liver injury.