外周血清游离核小体与SLE患者器官/系统损害的关联研究  

Association of serum soluble nucleosome with damage of organ or system in patients with systemic lupus erythematosus

作　　者：郝加虎[1] 张志华[2] 张国庆[2] 刘慧慧[2] 黄芬[2] 朱小明[1] 戴宏[3] 徐胜前[4] 叶冬青[2] 张学军[5] 

机构地区：[1]安徽医科大学公共卫生学院儿少卫生与妇幼保健学系,合肥230032 [2]安徽医科大学公共卫生学院流行病与卫生统计学系,合肥230032 [3]安徽医科大学第一附属医院肾脏内科,合肥230022 [4]安徽医科大学第一附属医院临床免疫科,合肥230022 [5]安徽医科大学皮肤病研究所,合肥230022

出　　处：《中国卫生检验杂志》2008年第2期229-233,共5页Chinese Journal of Health Laboratory Technology

基　　金：国家自然科学基金(30371247);安徽省高校省级自然科学研究项目(kj2007B148);安徽省高校青年教师科研资助计划(2004jq166;2007jq1067zd);安徽医科大学博士科研经费资助计划(XJ200602)

摘　　要：目的：比较系统性红斑狼疮患者（systemic lupus erythematosus,SLE）和正常对照两组间的血清可溶性核小体（serum soluble nucleosome）表达水平;分析血清核小体与SLE患者器官/系统损害之间的关系,并探讨血清核小体与患者器官/系统损害的关联是否涉及细胞凋亡。方法：运用流式细胞术,采用连接素V（Annexin V,AV）和碘化丙啶（propidiumiodide,PI）双染法检测研究对象的外周血单个核细胞（peripheral blood mononuclear cells,PBMCs）的早期凋亡率;以双抗夹心酶联免疫吸附实验测定外周血可溶性核小体及抗核小体抗体家族分子的表达水平。结果：SLE患者（n=76）血清核小体浓度（0.746±0.244）低于正常对照组（1.237±0.394）（t=9.112,P〈0.01）,且与抗核小体抗体浓度呈负相关（r=-0.458,t=4.434,P=0.000）;以正常对照组（n=69）血清核小体浓度均数的95%可信区间1.14～1.33作为核小体浓度正常范围,结果显示：SLE患者核小体减低组（A组,OD〈1.14,n=54）的发热、皮疹、C3降低、血沉（ESR）增高、管型、血尿、蛋白尿、anti-SSA等临床指标的阳性检出率显著高于核小体增高组（B组,OD≥1.33,n=22）,两组间差异有统计学意义（P分别为0.0001,0.0035,0.0164,0.0242,0.0171,0.0135,0.0001,0.0000）;SLE患者核小体减低组中疾病活动的阳性率（79.63%）高于核小体浓度增高组（45.45%）,两组间差异有统计学意义（χ2=8.65,P=0.0033）。结论：SLE患者血清核小体浓度可减低或增高,血清核小体浓度与抗核小体抗体水平呈显著负相关;血清核小体减低与SLE患者皮肤损害、肾损害的发生和疾病活动度密切相关。核小体在SLE尤其是狼疮性肾炎的发病中具有重要作用。Objective：To compare the expression of serum nucleosome by enzyme-linked immunosorbent assay between the healthy controls and patients with systemic lupus erythematosus（SLE） to analyze the relationship of the serum soluble nucleosome,the organ or system damage in SLE,and to define the role of apoptosis in the relationships.Methods：Annexin V（AV） and propidium iodide（PI） were used to detect the early apoptosis rate of peripheral blood mononuclear cells（PBMCs）.Serum soluble nucleosome levels as well as antinucleosome antibodies,anti-double-stranded DNA antibodies,and antihistone antibodies activities were assessed by Sandwich-enzyme-linked immunosorbent assay（ELISA）.Results：Patients with SLE（n=76） had a significantly lower level of serum soluble nucleosome（0.746±0.244） compared to normal healthy controls（1.237±0.394）（t=9.122,P〈0.01）.An inverse correlation was found between serum levels of nucleosome and serum antinucleosome antibodies in the entire group of SLE patients（r=-0.458,t=4.434,P=0.000）.Seventy-six of the 76 patients with SLE had serum levels of nucleosome over the range of normal（defined as the control mean±1.96SD）.Patients with SLE were divided into group A and group B according to the serum levels of nucleosome.Fifty-four SLE patients with OD value 〈1.14 were arbitrarily considered as expressing a low concentrations（group A,n=54）,and 22 with OD value ≥ 1.33 were classed as expressing a high concentrations（group B,n=22）.There was a significant difference in positive rate of fever between group A and group B（P=0.0001）.Similarly,we observed a significant difference in positive rate of skin eruption between group A and group B（P=0.0035）.The same was true when SLE patients with and without decreased complement factor 3（C3）, increased erythrocyte sedimentation rate（ESR）,cast,hematuria,proteinuria,anti-SSA antibodies（P=0.0164,0.0242,0.0171,0.0135,0.0001,0.0000,respectively） were analyzed.There was a higher positive rate of di

关 键 词：红斑狼疮 系统性 细胞凋亡 核小体 

分 类 号：R593.24[医药卫生—内科学]