类风湿关节炎成纤维滑膜细胞端粒保护蛋白TPP1及POT1 mRNA表达的研究

Expression of TPP1 and POT1 mRNA in synovial fibroblasts of patients with rheumatoid arthritis

目的检测端粒保护蛋白TPP1及POT1 mRNA在类风湿关节炎（RA）、骨关节炎（OA）患者及健康人成纤维样滑膜细胞（SFs）的表达水平，探讨其在RA发病机制中可能的作用。方法体外培养SFs，用实时荧光定量聚合酶链反应（PCR）方法检测28例RA、15例OA和3名健康者SFs TPP1，POT1 mRNA的表达水平，并与疾病活动性等临床指标进行分析。结果TPP1，POT1 mRNA在RA SFs组的表达低于OA组及健康对照组（P均〈0．05），OA组和健康对照组间差异无统计学意义。TPP1 mRNA在RA SFs的表达水平与RA患者抗环瓜氨酸肽（CCP）抗体及类风湿因子（RF）呈负相关（P均〈0．05），与疾病活动指数（DAS）、红细胞沉降率（ESR）、血清C反应蛋白（CRP）无相关性；POT1 mRNA表达与DAS、CCP、RF均无相关性。结论端粒保护蛋向TPP1、POT1基因表达的降低可能在RA SFs出现转化细胞特性中发挥重要作用；TPP1基因表达降低可能与RA出现关节侵蚀性改变密切相关。通过调整端粒保护蛋白TPP1、POT1基因的表达水平，有望为RA的治疗寻找新的靶点。

Objective To study the expression of telomeric protein TPP1 and POT1 mRNA and its association with disease stages and clinical manifestations in synovial fibroblast （SFs） from patients with rheumatoid arthritis （RA）, osteoarthritis （OA）, and healthy individuals in order to explore the mechanisms of pathogenesis of RA. Methods SFs were cultured in vitro, and TPP1 and POT1 mRNA were measured using real-time polymerase chain reaction （RT-PCR） in SFs. The expression of TPP1 and POT1 mRNA in SFs were compared between patients with RA （n=28）, patients with OA （n=15）, and healthy individuals （n=3）. Results The expression of TPP1 and POT1 mRNA in SFs in RA patients was significantly decreased when compared to OA patients and healthy individuals （P〈0.05）. The expression of TPP1 mRNA was found to be correlated negatively with anti-CCP antibodies and rheumatoid factor; but not correlated with Disease Active Score （DAS）, Serum C-reactive protein （CRP） level and erythrocyte sedimentation rate （ESR）. The expression of POT1 mRNA was not correlated with antibodies, rheumatoid factor, DAS, CRP and ESR. Conclusion Expression of TPP1 and POT1 mRNA in RA SFs is decreased significantly than that in OA and normal SFs. The low expression of TPPI mRNA may lead to dysfunction of telomere, and may be involved in the pathogenesis of RA and contributes to cartilage and bone destruction.