CAJ | 학술논문

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CⅡTAsiRNA对CIA具有治疗作用.
목적 장MHCⅡ류반식작용인자(CⅡTA) siRNA용우효원유도적소서관절염모형중,관찰시부구유치료효과.방법 장웅성DBA/1소서수궤분위효원유도성관절염(CIA)모형조、CⅡTA siRNA조(siCⅡTA조)、control siRNA조(siCT조)、정상조.재차면역후4주관찰소서발병정황,검측소서족조적종창도,병리절편관찰염증변화,MTT검측비림파세포대CⅡ효원적증식반응,실시형광정량PCR검측소서비세포IFN-γ、IL-4 mRNA표체수평,ELISA검측소서혈청중IFN-γ、IL-4、IL-17적함량.결과 siCⅡTA조관절염평분、비림파세포대Ⅱ형효원적증식반응저우모형조화siCT조；siCⅡTA조IFN-γ、IL-17수평저우모형조화siCT조,단IL-4수평고우모형조화siCT조.결론 미정맥고압주사CⅡTAsiRNA대CIA구유치료작용.
Objective To examine the therapeutic effect of C Ⅱ TA inhibition in collagen-induced arthritis(CIA),using a delivery system tailored to target C ⅡTA gene by small interfering RNA (siRNA).Methods Mice with collagen-induced arthritis were injected intravenously with C Ⅱ TA siRNA.The clinical score was monitored for up to 4 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-γ and IL-17 were elevated in CIA mice,but were iuhibited significantly by C Ⅱ TA 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.