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系统性红斑狼疮患者TH2型细胞因子受体表达及其基因多态性的研究

Expression of TH2 Cytokine Receptors and Relevent Gene Polymorphisms in Patients with Systemic Lupus Eythematosus

【作者】 姚煦

【导师】 李文忠; 陈志强; 胡兹嘉; 陈祥生;

【作者基本信息】 中国协和医科大学 , 皮肤病学与性病学, 2004, 博士

【摘要】 目的 初步研究三种Th2型细胞因子受体(IL-4R,IL-6R,IL-10R)在系统性红斑狼疮(SLE)发病机制中的作用及其潜在的临床意义,并探讨部分Th1和Th2型细胞因子受体基因多态性与SLE疾病易感性的关系。 方法 应用逆转录-聚合酶链反应(RT-PCR)检测89例SLE患者和30例健康对照者外周血单一核细胞(PBMC)的IL-4R、IL-6R和IL-10R mRNA的表达水平;用ELISA法检测受试者血清中IL-4、IL-6和IL-10水平。采用聚合酶链反应—单链构象多态性(PCR-SSCP)、聚合酶链反应限制性片段长度多态性(PCR-RFLP)和DNA测序方法进行IL-4R,IL-10R和IFNγR的基因多态性分析。 结果 Ⅰ.①活动期SLE患者、非活动期SLE患者及健康对照者IL-4R、IL-6R和IL-10R表达阳性率为100%。②PBMC的IL-4RmRNA表达水平:活动期SLE患者(1组)为0.60±0.147,非活动期SLE患者(2组)为0.40±0.13,健康对照者(3组)为0.37±0.07;1组和2组间比较有显著性差异(P<0.05),1组和3组间比较有显著性差异(P<0.05),2组和3组间比较无显著性差异(P>0.05)。PBMC的IL-6RmRNA表达水平:1组为0.90±0.27,2组为0.52±0.11,3组为0.57±0.24;1组和2组间比较有显著性差异(P<0.05),1组和3组间比较有显著性差异(P<0.05),2组和3组间比较无显著性差异(P>0.05)。PBMC的IL-10RmRNA表达水平:1组为0.87±0.29,2组为0.72±0.21,3组为0.68±0.14;1组和2组间比较有显著性差异(P<0.05),1组和3组间比较有显著性差异(P<0.05),2组和3组间比较无显著性差异(P>0.05)。SLE患者外周血PBMC的IL-4R、IL-6R和IL-10R mRNA的表达量与SLEDAI积分呈正相关性,具有统计学意义(r值分别为0.500、0.421和0.244,P值均小于0.05)。

【Abstract】 Objective To investigate the roles of Th2 cytokine receptors in the pathogenesis of systemic lupus erythematosus (SLE). To assess the correlation between the polymorphisms of some Th2 /Th1 cytokine receptor genes and susceptibility of SLE in Chinese Han nationality.Methods RT-PCR technique was used to semiquantititively analyze the mRNA expression of IL-4R, IL-6R and IL-10R in PBMC from 89 patients with SLE and 30 healthy controls. Double antibody sandwich ELISA was applied to determine the serum levels of three Th2 cytokines. Genotypes of IL4RA, IL10RA and IFNGR were examined by the reverse transcription-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) method and DNA sequencing.Results The mRNA expression of Th2 cytokine receptors was positively detected in 100% of subjects, including active SLE group(group Ⅰ), inactive SLE group(group Ⅱ) and healthy control group(groupⅢ). The mean level of IL-4R mRNA expression in group Ⅰ , Ⅱ or Ⅲ was 0.604±0.147, 0.40±0.13 or 0.37±0.07, respectively. Compared with group Ⅱ or group Ⅲ, the mean level of IL-4R mRNA expressions was markedly increased in group Ⅰ (P<0.05), with non-statistical difference between group Ⅱ and groupⅢ (P=0.315). The mean level of IL-6R mRNA expressions in group I , II or III was 0.902±0.273, 0.519±0.11 or 0.573±0.24, respectively. Compared with group Ⅱ or group Ⅲ, the mean level of IL-6R mRNA expression in group Ⅰ was markedly increased (P<0.05), with non-statistical difference between group Ⅱ and group Ⅲ (P=0.289). The mean levels of IL-IOR mRNA expression in

  • 【分类号】R593.241
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