中文摘要：

目的将MHCⅡ类反式作用因子（CⅡTA）siRNA用于胶原诱导的小鼠关节炎模型中，观察是否具有治疗效果。方法将雄性DBA／1小鼠随机分为胶原诱导性关节炎（CIA）模型组、CⅡTA siRNA组（siCⅡTA组）、control siRNA组（siCT组）、正常组。再次免疫后4周观察小鼠发病情况，检测小鼠足爪的肿胀度，病理切片观察炎症变化，MTT检测脾淋巴细胞对CⅡ胶原的增殖反应，实时荧光定量PCR检测小鼠脾细胞IFN-γ、IL-4 mRNA表达水平，ELISA检测小鼠血清中IFN-γ、IL-4、IL-17的含量。结果siCⅡTA组关节炎评分、脾淋巴细胞对Ⅱ型胶原的增殖反应低于模型组和siCT组；siCⅡTA组IFN-γ、IL-17水平低于模型组和siCT组，但IL-4水平高于模型组和siCT组。结论尾静脉高压注射CⅡTA siRNA对CIA具有治疗作用。

英文摘要：

Objective To examine the therapeutic effect of C Ⅱ TA inhibition in collagen-induced arthritis（ CIA）, using a delivery system tailored to target C Ⅱ TA gene by small interfering RNA （siRNA）. Methods Mice with collagen-induced arthritis were injected intravenously with C ⅡTA siRNA. The clinical score was monitored for up to g weeks after treatment. The severity of inflammation of mouse joint was evaluated by histological examination. Real-time PCR was used to determine the cytokine mRNA expression. Cytokine production was measured by ELISA from serum. T cell proliferation was examined by MTT method. Results IFN-γand IL-17 were elevated in CIA mice, but were inhibited significantly by C ⅡTA siRNA either prevention or intervention of autoimmune arthritis. Collagen specific T cell proliferation was significantly suppressed. Increased level of IL-4 by T cells was observed in C Ⅱ TA siRNA treated group compared with that of control group. Conclusion Our findings indicate that systemic RNAi-mediated C Ⅱ TA gene silencing is effective in the treatment of CIA and regulateds the balance of Th1/Th2 differentiation.