肾综合征出血热外周静脉血细胞因子的变化与病情的关系

Changes of plasma cytokines in hemorrhagic fever with renal syndrome

目的观察肾综合征出血热（HFRS）患者各病期外周静脉血血管内皮生长因子（VEGF）、可溶性血管内皮生长因子受体2（sVEGFR2）、血管生成-素1（ANG-1）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平的变化及其变化与病程中血管渗漏的关系,为研究HFRS的发病机制提供依据。方法用酶联免疫吸附法（ELISA）检测了68例不同病期HFRS患者外周静脉血上述5种细胞因子,并以20例健康志愿者作为正常对照。同时对20例HFRS患者病程5期连续动态收集的外周静脉血标本中的VEGF进行了测定。结果在所有观察患者中,血浆VEGF水平从发热期开始增高[（337.6±238.0）ng/L],休克期达到峰值[（556.0±185.2）ng/L],少尿期开始迅速下降[（259.0±152.8）ng/L],在多尿期[（223.1±110.6）ng/L]和恢复期[（246.5±202.0）ng/L]回落到正常水平。HFRS患者sVEGFR2、ANG-1水平在休克、少尿、多尿期均低于健康对照组;TNF-α和IFN-γ水平在发热期、低血压休克期、少尿期和多尿期均高于健康对照组,其中大多数与后者比较差异有统计学意义。此外,对20例各病期连续动态采集的血样进行验证检测表明,VEGF在休克期表达确实明显升高[（561.1±194.3）ng/L],与其他各期（212.5~397.5 ng/L）比较差异均有统计学意义。结论 HFRS患者血管通透性增高可能与休克期VEGF高表达有关,sVEGFR2、ANG-1、TNF-α、INF-γ表达量的变化可能在VEGF介导的血管通透性增高中发挥协同作用。

Objective To explore changes of vascular permeability involved plasma cytokines,including vascular endothelial growth factor（VEGF）,soluble vascular endothelial growth recepter 2（sVEGFR2）,angiopoitin-1（Ang-1）,tumor necrosis factor-α（TNF-α）and interferon（IFN-γ） in patients of hemorrhagic fever with renal syndrome（HFRS）.Methods Plasma samples were collected from 68 HFRS patients of different disease stages and 20 healthy volunteers.The concentrations of cytokines were determined by sandwich enzyme-linked immunosorbent assay（ELISA）.Results The concentration of plasma VEGF increased to（337.6±238.0）ng/L at the stage of febrile,reached to（556.0±185.2）ng/L at the stage of hypotensive/shock,then sharply decreased to（259.0±152.8）ng/L at the stage of oliguric and maintained at normal level at stages of polyuric and convalescent in HFRS patients（P〈0.05）.The pattern of VEGF changes at different stages of HFRS were further confirmed in 20 HFRS patients with dynamical observation.The concentrations of sVEGFR2,ANG-1,TNF-α and INF-γ varied at the different stages of HFRS.Conclusions These results suggest that VEGF may play an important role in vascular permeability at the stages of hypotensive/shock in HFRS patients,and sVEGFR2,ANG-1,TNF-α and INF-γ may have synergetic or antagonistic effects on VEGF-mediated micro-vascular permeability.