类风湿关节炎(Rheumatoid arthritis，RA)是一种以慢性炎症性关节病变为特点的自身免疫性疾病，特征性表现为关节疼痛、肿胀、晨僵，如不能及早控制控制病情，可引起关节结构的严重破坏，最终导致患者残疾，其症状发作时可严重影响患者的劳动能力和生活质量，是威胁人类健康的重要疾病之一。RA的发病的分子机制一直是研究的热点、难点。细胞因子信号抑制因子3(SOCS3)是STAT抑制因子(SSI)蛋白家族的成员，可作为STAT细胞因子信号通路的负调控因子，类风湿关节炎患者的滑膜细胞中存在过量表达。 目的：本研究旨在阐明SOCS3基因表达在大鼠类风湿关节炎模型中成纤维细胞样滑膜细胞增殖和凋亡中的作用。 方法：本研究采用20只佐剂诱导类风湿关节炎的Lewis大鼠，随机分为实验组和对照组，28天后处死实验组大鼠，收集第三代成纤维细胞样滑膜细胞，通过慢病毒表达系统将基因转导入细胞，根据转导基因不同分为实验组(SOCS3组)、对照组(空载体组)和空白组。采用MTT比色法检测细胞活力；采用流式细胞术分析细胞凋亡情况；采用酶联免疫吸附试验检测炎症因子白介素-2(IL-2)，干扰素-γ(IFN-γ)和肿瘤坏死因子(TNF-α)表达情况；采用RNA干扰技术沉默细胞中内源SOCS3的表达，检测SOCS3缺失对细胞增殖造成的影响。 结果：与对照组和空白组相比，SOCS3表达组细胞增殖加强，凋亡减少，炎症因子IL-2、IFN-γ和TNF-α表达增多；在细胞内沉默SOCS3的表达，则抑制了细胞的增殖。本研究表明，SOCS3因子在大鼠类风湿关节炎模型可以显著促进成纤维细胞样滑膜细胞活力，抑制细胞凋亡。 结论：1.在大鼠佐剂型类风湿关节炎模型中，慢病毒介导的SOCS3过量表达可使FLS；2.在大鼠佐剂型类风湿关节炎模型中，慢病毒介导的SOCS3过量表达抑制了FLS细胞发生凋亡；3.在大鼠佐剂型类风湿关节炎模型中，慢病毒介导的SOCS3过量表达可使炎症因子白介素-2(IL-2)、干扰素-γ(IFN-γ)和肿瘤坏死因子(TNF-α)表达。4.在大鼠佐剂型类风湿关节炎模型中，利用慢病毒沉默SOCS3表达抑制了FLS的增殖。 综上所述，本研究不仅在动物、细胞和分子三个水平探究了SOCS3在RA中扮演的角色，并且提示SOCS3是治疗RA的潜在作用靶点。 关键词：SOCS3，类风湿关节炎，慢病毒载体，增殖，凋亡

 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory arthropathy. It usually characterized by as pain , swelling and moring stiffness of the joints. Failure to control the disease may eventually lead to serious destruction of the joint structure and deformity. The infiltration of immune cells in the synovium of the joints is its pathological basis. Symptoms may severely affect the work ability and survival of patients. RA is one of the most important diseases threatening human health. The molecular mechanism of RA has always been the focus and difficulty of research. Human SOCS3 is a member of the STAT inhibitory factor (SSI) protein family. It can be used as a negative regulator of STAT cytokine signaling pathway and is overexpressed in synovial cells of patients with RA. It has been proved that high expression of SOCS3 can slow down the progression of RA. Aim: The aim of this study was to elucidate the role of SOCS3 gene expression in the proliferation and apoptosis of fibroblasts-like synoviocytes in rat RA model. Methods:In this study, 20 Lewis rats with RA induced by adjuvant were randomly divided into experimental group and control group. 28 days later, rats in experimental group were executed. The third generation of fibroblasts-like synoviocytes were collected and transfected into cells by Lentivirus Expression system. According to the different transduction genes, they were divided into SOCS3 group, control group and blank group. MTT colorimetric assay was used to detect cell viability; flow cytometry was used to analyze cell apoptosis; enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factors interleukin-2 (IL-2), interferon-gamma (IFN--γ)) and tumor necrosis factor (TNF-α );RNA interference was used to silence the expression of endogenous SOCS3 in cells and detect the effect of SOCS3 deletion on cell proliferation. Result: The results showed that compared with the control group and the blank group, the expression of SOCS3 in SOCS3 group increased, and the cells apoptosis decreased. The expression of inflammatory factors DL-2, IFN-γ and TNF-α increased, while silencing the expression of SOCS3 inhibited cell proliferation. This study shows that SOCS3 can significantly promote the proliferation of synovial fibroblasts and inhibit apoptosis in rat rheumatoid arthritis model, thus aggravating the progress of RA. Conclusion: 1. Overexpression of SOCS3 mediated by lentivirus stimulates the proliferation of FLS in rat adjuvant rheumatoid arthritis model; 2. Overexpression of SOCS3 mediated by lentivirus inhibits the apoptosis of FLS cells in rat adjuvant rheumatoid arthritis model; 3. Overexpression of SOCS3 mediated by lentivirus stimulates the expression of inflammatory factors (IL-2, IFN-γ and TNF-α) in rat adjuvant rheumatoid arthritis model; 4. In the rat model of adjuvant rheumatoid arthritis, silencing the expression of SOCS3 mediated by lentivirus inhibited the proliferation of FLS. Keywords: SOCS3, rheumatoid arthritis, lentiviral vector, proliferation, apoptosis