中文摘要：

【摘要】目的分析关节内注射和联合静脉注射间充质干细胞（MSC）对实验性类风湿性关节炎（RA）的疗效，并分析相关机制。方法胶原诱导的RA模型大鼠，采用关节内注射MSC、经静脉注射MSC及关节内注射联合静脉注射MSC治疗，通过后肢体积、关节炎指数，炎症关节的病理检查评价治疗效果，通过动物血浆内TNF-α及IL-10检测及MSC与大鼠脾脏淋巴细胞共培养分析MSC治疗的相关机制。结果关节内注射MSC或静脉注射MSC均可降低实验性RA模型大鼠的关节炎指数，且二种方法具有协同作用，病理检查证明MSC治疗后RA模型的软骨破坏减轻。ELISA检测显示MSC治疗后RA动物模型血浆促炎细胞因子TNF-α的水平显著降低，而抑炎细胞因子IL-10的水平显著升高，同时共培养实验表明MSC可显著抑制II型胶原诱导的T淋巴细胞增殖。结论MSC可有效治疗实验性RA，治疗作用与MSC的免疫抑制作用相关。

英文摘要：

Objective To analyze the therapeutic effects of intra-articular injection of mesenchymal stem cells （ MSCs ） combined with systemic injection of MSCs in treating experimental rheumatoid arthritis, and the underlying mechanism. Methods Collagen-induced arthritis models were established using rats, then these models were treated by intra-articular injection of MSCs, systemic injection of MSCs, and intra-articular injection combined with systemic injection of MSCs. And the therapeutic effects were evaluated by measuring the hind limb volumes, arthritis indices, and pathological examination of inflamed joints. The underlying mechanisms were analyzed by detecting plasma levels of tumor necrosis factor- α （TNF-α） andlnterleukin-10 （IL-10） ofratmodels, and coculturing MSCs and spleen lymphocytes from rat models. Results Bothintra-articular and systemic injection of MSCs can significantly lower arthritis indices of experimental rheumatoid arthritis models, and there were synergistic effects between the two ways of injection. Pathologic analysis demonstrated that cartilage destruction of animal models was less severe after MSCs treatment. ELISA assays indicated that the levels of pro-inflammatory cytokines, TNF-α, decreased significantly, and levels of anti-inflammatory cytokines, IL-10, increased significantly. Coculture of MSCs and spleen lymphocytes demonstrated that MSCs significantly inhibited type II collagen induced proliferation of T lymphocytes. Conclusions MSCs have significant therapeutic effects on experimental rheumatoid arthritis, which is related to their immunosuppressive effect.