中性粒细胞胞外诱捕网在恶性肿瘤患者PICC相关深静脉血栓形成中的作用

Role of neutrophil extracellular traps in PICC-associated deep venous thrombosis in patients with malignant tumor

目的研究中性粒细胞胞外诱捕网(NETs)在恶性肿瘤患者外周中心静脉导管(PICC)相关深静脉血栓形成(DVT)中的作用。方法选取恶性肿瘤PICC置管患者77例,根据是否发生PICC相关DVT分为DVT组(n=27)和无DVT组(n=50)。比较2组血浆NETs水平,病变静脉与外周静脉血浆NETs水平,肝素应用前和应用后0.5、1、2 h血浆NETs水平;并以HE染色与免疫荧光染色法观察血栓中NETs相关情况。结果DVT组血浆NETs水平高于无DVT组(P<0.05)。DVT组病变静脉血浆NETs水平高于外周静脉(P<0.05)。无DVT组PICC置管侧血浆NETs水平与外周静脉相比,差异无显著意义(P>0.05)。肝素应用后0.5 h,血浆NETs水平高于应用前(P<0.05),应用后1、2 h呈降低趋势。HE染色显示血栓中有大量白细胞与纤维蛋白网,白细胞主要为中性粒细胞;免疫荧光染色显示血栓中存在大量DNA网络、NETs和中性粒细胞。结论NETs在恶性肿瘤PICC相关DVT患者外周血与病变静脉中呈高表达水平,且DVT不仅含纤维蛋白原,亦含有NETs DNA网络等成分,可能成为血栓类疾病治疗的新靶点。

AIM To investigate the role of neutrophil extracellular traps(NETs)in peripherally inserted central venous catheter(PICC)-associated deep venous thrombosis(DVT)of patients with malignant tumors.METHODS Seventy-seven patients with malignant tumor PICC were enrolled.According to whether or not PICCassociated DVT occurred,patients were divided into DVT group(n=27)and no DVT group(n=50).Plasma NETs levels between two groups,plasma NETs levels in the diseased venous and peripheral vein,and plasma NETs levels before,and 0.5,1 and 2 h after heparin application were compared.HE staining and immunofluorescence staining were used to observe the NETs in the thrombus.RESULTS The plasma NETs level in the DVT group was higher than that in no DVT group(P<0.05).The diseased venous plasma NETs level was higher than that in the peripheral vein(P<0.05)in the DVT group.There was no significant difference in the plasma NETs level between the PICC and the peripheral vein(P>0.05)in the no DVT group.The level of plasma NETs at 0.5 h after heparin application was higher than that before application(P<0.05),and decreased at 1 and 2 h after application.HE staining showed a large number of white blood cells and fibrin network in the thrombosis,and white blood cells were mainly neutrophils.Immunofluorescence staining showed that there were a large number of DNA networks,NETs and neutrophils in the thrombosis.CONCLUSION NETs is highly expressed in peripheral blood and diseased venous of patients with malignant tumors with PICC-associated DVT.DVT contains not only fibrinogen,but also NETs DNA network,which may become a new target in the treatment of thrombotic diseases.