系统性硬化患者HMGB1和sRAGE表达及其临床意义  

Expression and clinical significance of HMGB1 and sRAGE in patients with systemic sclerosis

作　　者：徐雪[1] 楚海燕[2] 梁敏锐[1] 吴文育[3] 王久存[2] 邹和建[1] 

机构地区：[1]复旦大学附属华山医院风湿科 [2]复旦大学生命科学院 [3]复旦大学附属华山医院皮肤科,上海200040

出　　处：《现代免疫学》2012年第2期120-125,共6页Current Immunology

摘　　要：研究系统性硬化(systemic sclerosis,SSc)患者体内高迁移率族蛋白B1(HMGB1)和可溶性晚期糖基化终产物受体(sRAGE)蛋白和基因表达水平,探讨这两种炎症性蛋白在SSc发病过程中的作用。收集肢端型硬皮病(lSSc)30例、弥漫型硬皮病(dSSc)30例和正常人40例。运用ELISA方法检测血浆中HMGB1、sRAGE的含量,用real-time PCR方法检测外周血细胞中这两个因子的mRNA相对表达量,并对临床和实验室指标进行相关分析。与正常对照组相比,lSSc和dSSc患者血浆HMGB1含量[(150.31±65.52)μg/L,(151.07±81.32)μg/L],高于正常对照组(112.89±60.57)μg/L(P均<0.05);两组患者血浆sRAGE[(395.06±158.38)ng/L,(425.57±212.35)ng/L]水平高于对照组(329.47±107.03)ng/L(P均<0.05)。两组患者血浆HMGB1和sRAGE的浓度分别两两之间存在正相关(r=0.349,P<0.05;r=0.211,P<0.05)。两种类型硬皮病患者外周血细胞HMGB1mRNA相对表达量均高于正常对照组(P均<0.05),而sRAGE mRNA相对表达量较对照组均无明显差异。伴有累及肺部或肾脏的SSc患者血浆HMGB1、sRAGE水平明显高于无累及肺部或肾脏的患者(P均<0.05);抗组蛋白抗体或抗RNA聚合酶Ⅲ抗体阳性的SSc患者血浆HMGB1、sRAGE水平明显高于抗体阴性组,而抗着丝点抗体阳性组SSc患者血浆HMGB1、sRAGE水平低于抗体阴性组患者(P<0.05)。HMGB1和sRAGE在系统性硬化患者体内表达明显升高,提示患者体内存在着明显的炎症反应,且这两个蛋白含量与某些临床实验室指标有显著相关性,表明其可能在疾病的发病机制中起着一定重要作用,可望成为评价疾病严重性的新指标。To determine the protein and gene levels of HMGB1 and sRAGE in the patients with systemic sclerosis, to analyze their clinical significance, thirty limited systemic scleroderma patients（ISSc） and thirty diffuse systemic scleroderma patients （dSSc） were recruited and forty healthy volunteers were recruited as normal controls. Plasma protein and mRNA levels of HMGB1 and sRAGE in peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA） and real-time RT- PCR respectively. To further explore the relationship between HMGB1/sRAGE and clinical or laboratory indexes of scleroder- ma patients. The plasma concentrations of HMGB1 and sRAGE were significantly increased in dSSc and 1SSc patients as com- pared to the normal controls （P〈0.05）. The levels of plasma HMGB1 showed a positive correlation with the levels of plasma sRAGE in both 1SSc and dSSc patients. The relative mRNA levels of HMGB1 were elevated in both kinds of patients compared to normal controls. The levels of plasma HMGB1 and sRAGE were significantly increased in SSc patients with involve of lung or kidney than those without involve of lung or kidney （P〈0.05）. Meanwhile, the levels of plasma HMGB1 and sRAGE were significantly increased in SSc patients with anti-histone antibody-positive group or anti-RNA polymerase III antibody positive group than the antibody-negative groups. However, the levels of plasma HMGB1 and sRAGE were significantly decreased in SSc patients with anti-centromere antibody positive group than antibody-negative group. Both HMGB1 and sRAGE expression levels in SSc patients are significantly elevated and the close relationship between HMGB1 and sRAGE levels and several clinical and laboratory indexes suggests that the two protein may play an important role in the pathogenesis of scleroderma and may be a promising target to assess the activity of disease.

关 键 词：硬皮病、肢端型、弥漫型 HMGB1、sRAGE MRNA 相关性 

分 类 号：R593.24[医药卫生—内科学]