【作者】 王超；

【导师】 叶冬青；

【作者基本信息】 安徽医科大学 ， 流行病与卫生统计学， 2011， 硕士

【摘要】 目的探讨人肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)在系统性红斑狼疮(systemic lupus erythematosus,SLE)发病中的作用,通过检测外周血TWEAK的血清水平及mRNA表达水平,研究TWEAK的表达情况与系统性红斑狼疮患者临床与实验室特征的关联,从而为揭示TWEAK在SLE的发病中可能存在的作用提供依据。方法选取安徽医科大学附属省立医院风湿免疫科的门诊及住院部系统性红斑狼疮患者组成病例组,随机抽取安徽医科大学第二附属医院健康体检中心的健康志愿者作为正常对照组。采用1997年美国风湿病学会修订的SLE分类标准作为诊断依据。在本课题中,共对33例SLE病人和15例健康对照进行了外周血白细胞中TWEAK mRNA的表达水平的检测,方法选用荧光定量聚合酶链反应(Fluorescent quantitative polymerase chain reaction, FQ-PCR)法;对62例SLE病人和15例正常对照的外周血清TWEAK浓度进行了检测,方法选用双抗体夹心酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)。调查获得研究对象知情同意后,抽取外周静脉血。收集患者一般情况和临床资料,同时进行SLE疾病活动指数(SLE disease activity index, SLEDAI)评分。实验所得数据用SPSS10.01进行统计分析,符合正态分布的两组间定量资料比较采用t检验;如不符合正态分布,采用Mann-Whitney秩和检验。资料符合双变量正态分布的两组间定量资料相关性分析,采用Pearson相关分析;如不符合正态分布,选取Spearman等级相关分析。检验水准α=0.05。结果FQ-PCR结果显示SLE病人外周血单个核细胞中TWEAK的mRNA表达水平低于正常对照水平(P=0.001),活动组低于非活动组(P=0.025),然而狼疮肾炎组与狼疮非肾炎组差异无统计学意义(P=0.614)。ELISA结果表明SLE患者血清中TWEAK的浓度高于正常对照组(P<0.001)。另外,血管炎组高于非血管炎组(P=0.002),狼疮头痛组高于非狼疮头痛组(P=0.024),但是狼疮肾炎组与非肾炎组(P=0.989),活动组与非活动组(P=0.961)差异无统计学意义。结论本研究发现病例组TWEAK的mRNA表达水平较对照组偏低,但血清TWEAK水平在SLE患者中升高,并且血管炎组高于非血管炎组,狼疮头痛组高于非狼疮头痛组,提示TWEAK可能与SLE发病相关。更多还原

【Abstract】 Objective The aim of this study was to compare the mRNA and serum expression of Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in patients with systemic lupus erythematosus (SLE) and healthy controls.Methods SLE patients were in- and out-patients of the Rheumatology Department in the Anhui Provincial Hospital. Age and sex-matched healthy controls were recruited at the second Affiliated Hospital, Anhui Medical University. Diagnosis of SLE was established according to the 1997 revised criteria of American College Rheumatology (ACR). Disease activity was evaluated using the SLE Disease Activity Index (SLEDAI) score. 62 patients and 15 healthy controls were recruited in the study. TWEAK messenger RNA (mRNA) expression in PBMC from 33 of 62 patients was detected by relative quantitation FQ-PCR. TWEAK concentrations in serum of all 62 patients were measured by Enzyme linked immunosorbent assay (ELISA).The data were analyzed by the SPSS 10.01 software. Quantitative variables were described using mean±SD. Data in which variables demonstrated nonparametric distributions were expressed as median with interquartile range (IQR), and analyzed by Mann-Whitney U test for unpaired samples. Other data were analyzed with Student’s t test for unpaired values to compare differences between different control cultures. Pearson correlation or Spearman correlation were used to analyze the correlation between two continuous variables. A p value < 0.05 was considered statistically significant.Results TWEAK mRNA expressions in PBMC were decreased in SLE patients compared with healthy controls (P=0.001). Lower TWEAK mRNA expression was also found in the active SLE patients when compared to inactive counterparties (P=0.025). However, there is no significant difference between LN patients and non-LN SLE patients (P=0.614). The serum level of TWEAK (sTWEAK) in SLE patients was increased when compared to healthy controls (P<0.001). In addition, the sTWEAK level was higher in SLE patients with vasculitis than that in SLE patients without vasculitis (P=0.002), the same was true in comparison between patients with and without headache (P=0.024). Nevertheless, no significant differences were found between active SLE patients and inactive patients (P=0.961), as well as between LN patients and non-LN SLE patients (P=0.989).Conclusions In our study, SLE patients express reduced TWEAK mRNA but elevated level of sTWEAK, in addition, sTWEAK level was associated with several clinical manifestations of SLE, indicating that TWEAK may play a complex role in SLE.更多还原