高迁移率族蛋白B1与维持性血液透析患者微炎症及内皮损伤的相关性探讨

High mobility group box protein-1 correlating with microinflammation and endothelial dysfunction in patients on chronic intermittent hemodialysis

目的本研究通过观察分析维持性血液透析(maintenance hemodialysis,MHD)患者血清高迁移率族蛋白B1(high mobility group box protein-1,HMGB1)水平的变化,初步探讨其与炎症因子、内皮损伤标志物的关系,了解HMGB1对MHD患者微炎症状态及血管内皮的影响。方法采用横断面研究方式,选择MHD患者89例,并以31例健康者作对照,酶联免疫吸附法(enzyme-linked immunosorbentassay,ELISA)检测入选者血清肿瘤坏死因子á(tumor necrosis factor-á,TNF-á)、白细胞介素6(interleukin-6,IL-6)和HMGB1水平。ELISA法检测MHD患者血清可溶性血管细胞黏附分子1(soluble vas-cular cell adhension molecule-1,sVCAM-1)和E选择素水平,同时收集其血常规和血生化等指标。结果 MHD患者血清HMGB1、TNF-á和IL-6水平均显著高于正常对照组(P<0.01),HMGB1水平与TNF-á、IL-6呈正相关(相关系数分别为0.711和0.804,均P<0.01)。HMGB1水平与sVCAM-1、E选择素水平呈正相关(相关系数分别为0.454和0.601,均P<0.01),与血红蛋白和白蛋白呈负相关(相关系数分别为-0.260和-0.372,均<0.05),与总胆固醇、甘油三酯及血糖等不相关(P>0.05)。结论 MHD患者血清HMGB1水平升高,与血管内皮损伤密切相关,因此其作为一项评价MHD患者微炎症状态的新指标具有临床应用价值。

Objective High mobility group box protein-1 （HMGB1） is a newly recognized molecule behaving as an important extracellular mediator in systemic inflammation. Systemic inflammation results in endothelial cell activation and vascular injury. In the present study, we determined serum HMGB1 level in patients on maintenance hemodialysis （MHD）, and assessed the HMGB1 level in association with microinflammation biomarkers and endothelial dysfunction. Methods During the period of March 2009 through April 2009, 89 patients （46 male, 43 female, mean age 56.54±10.72 years） with end stage renal dysfunction on MHD （for 65.2±54.7 months） as well as 31 healthy volunteers were investigated. Their disease status was stable, and they had no evidence of vascular disease and/or active infection. Serum levels of HMGB1, TNF-ásVCAM1 and E-selectin were measured by ELISA. Results Serum HMGB1 in patients was 5.10±1.93ì/L, significantly higher than that in healthy volunteers （2.20±0.31ì/L, n=31）. Serum HMGB1 positively correlated with TNF-á（r=0.711, P〈0.01）, IL-6 （r=0.804, P〈0.01）, soluble vascular cell adhesion molecule 1 （sVCAM1） （r=0.454, P〈0.01）, and E-selectin （r=0.601, P〈0.01）, but negatively correlated with Hb （r=0.26, P=0.013） and Alb （r=0.372, P〈0.01）. Serum HMGB1 did not correlate with total cholesterol, triglyceride and blood glucose. Conclusions Higher serum HMGB1 was frequently found in MHD patients, probably reflecting the vascular endothelial injury in these patients. Therefore, serum HMGB1 may be used clinically as a microinflammation biomarker in MHD patients.