洪宏海++王征++夏勇

【摘 要】目的：探讨长非编码RNA MT1JP调控p53抑制类风湿关节炎炎症反应的作用及机制。

方法：qRT-PCR法检测类风湿关节炎患者和骨关节置换患者滑膜组织中长非编码RNA MT1JP相对表达；小分子干扰RNA干扰MT1JP研究其作用；ELISA检测炎症因子白细胞介素（IL）-1β、IL-6、IL-8水平；Western blot检测p53蛋白水平。结果：类风湿关节炎患者滑膜组织MT1JP水平明显低于骨关节置换患者，且类风湿关节炎患者滑膜组织MT1JP水平与血清中炎症因子IL-1β、IL-6、IL-8水平呈负相关；干扰MT1JP后明显促进MH7A滑膜细胞的IL-1β、IL-6、IL-8分泌和抑制p53表达。结论：类风湿关节炎患者滑膜组织MT1JP水平下调，通过调控p53进而促进炎症因子的分泌和炎症反应。

【关键词】 关节炎，类风湿；MT1JP；炎症因子；p53

The Role and Mechanism of Long Noncoding RNA MT1JP Regulating p53 to Inhibit Inflammatory Reaction of Rheumatoid Arthritis

HONG Hong-hai，WANG Zheng，XIA Yong

【ABSTRACT】Objective：To study the role and mechanism of long noncoding RNA MT1JP regulating p53 to inhibit inflammatory reaction of rheumatoid arthritis.Methods：The qRT-PCR method was used to detect the relative expression of long noncoding RNA MT1JP in patients with rheumatoid arthritis or having undergone bone joint replacement.Small molecules interfered RNA to interfere MT1JP to study the effects.ELISA was used to detect the levels of（IL）-1β，IL-6 and IL-8.Western blot was used to detect the protein level of p53.Results：The levels of MT1JP in synovial tissue of patients with rheumatoid arthritis was significantly lower than that in patients with bone and joint replacement surgery，and the levels of MT1JP in patients with synovial tissue were negatively correlated with inflammatory factor IL-1β，IL-6 and IL-8.after interference，the secretion of IL-1β，IL-6 and IL-8 in MH7A synovial cells were enhanced，and expression of p53 was inhibited.Conclusion：The level of MT1JP in synovial tissue of rheumatoid arthritis is down regulated，which can promote the secretion of inflammatory factors and inflammatory response by regulating p53.

【Keywords】 arthritis，rheumatoid；MT1JP；inflammatory factors；p53

类风湿关节炎（rheumatoid arthritis，RA）是一种自身免疫性疾病，其病理特征为炎症反应和炎症因子分泌增多。RA临床表现为长期慢性炎症浸润、关节疼痛、关节肿大和畸形[1]。女性RA发病率约为1.16%，明显高于男性的0.44%[1]。RA的具体发病机制目前还不清楚。炎症反应过度激活是RA最重要的致病机制[2]。文献报道，肿瘤坏死因子-α（TNF-α）、LPS等促炎因子刺激关节滑膜细胞后激活核转录因子-κB（NF-κB）信号通路，随后诱导白细胞介素（IL）-6、IL-8、IL-1β和基质金属蛋白酶（MMPs）表达，最终导致关节炎症反应和骨关节破坏[3]。敲除IL-1或阻断IL-6明显改善RA动物模型中炎症浸润和软骨破坏[4]。因此，寻找新的靶点来抑制炎症因子分泌和炎症反应对治疗RA尤为重要。

长非编码RNA是一类普遍存在于哺乳动物，长度 > 200 bp的非编码RNA。长非编码RNA有着广泛的生物学功能，如调控基因转录和翻译，蛋白质定位，细胞结构完整性，细胞周期和炎症反应