肌内注射rAAV2/rTNFR：Fc对大鼠胶原性类风湿关节炎模型的治疗作用  

Anti-Inflammatory Effect of Intramuscular rAAV2/rTNFR:Fc Gene Transfer on Collagen Induced Arthritis in Rats

作　　者：周晓冰[1] 高凯[1] 沈连忠[1] 赵爱志 康禹[2] 王刚 吴小兵 王军志[1] 李波[1] 

机构地区：[1]中国药品生物制品检定所国家药物安全评价监测中心,北京100083 [2]本元正阳基因股份公司,北京100176

出　　处：《中国药学杂志》2011年第7期507-511,共5页Chinese Pharmaceutical Journal

基　　金：国家“十五”863资助项目(2002AA2Z3421)

摘　　要：目的观察肌肉注射2型重组腺相关病毒/肿瘤坏死因子受体:IgG1FC融合基因(rAAV2/rTNFR:Fc)对大鼠类风湿关节炎模型的治疗作用。方法皮内注射Ⅱ型胶原乳剂,诱发胶原性大鼠类风湿关节炎模型。将大鼠随机分为5组,每组10只,包括:正常对照组、模型对照组、载体对照组、地塞米松对照组和rAAV2/rTNFR:Fc肌肉注射给药组。观察各组大鼠的关节炎指数(AI)、关节肿胀程度、踝关节的X线变化、组织病理改变与动物血清肿瘤坏死因子(TNF)-α及其受体(TNFR)水平。结果与模型对照和载体对照组比较,肌肉注射rAAV2/rTNFR:Fc可使关节炎症明显减轻,AI降低、关节肿胀程度减轻;X线检查显示rAAV2/rTNFR:Fc给药组关节结构清晰,无明显骨质破坏。组织病理检查结果也表明,给药组关节腔内滑膜增生和炎性细胞浸润程度减轻,增生的血管翳肉芽组织减少;此外,与模型对照组和载体对照组比较,给药组血清中TNF-α水平显著下降(P<0.05),而TNFR水平明显上升(P<0.05)。结论肌肉注射给予rAAV2/rTNFR:Fc对大鼠胶原性类风湿关节炎模型具有明显的抗炎作用。OBJECTIVE To investigate the effect of intramuscular rAAV2/rTNFR：Fc gene transfer on collagen induced arthritis in rats.METHODS An experimental arthritis model was induced by intradermal injection of Ⅱ type collagen.All rats were randomly divided into five groups（10 animals per group） including normal,model,vector,dexamethasone control group and rAAV2/rTNFR：Fc-treated group.Arthritis was evaluated by arthritis index,paw swelling,radiographic and histological examination.The serum TNF-α and TNFR level were determined.RESULTS Compared with the model and vector control group,anti-inflammatory effect was observed in the rAAV2/rTNFR：Fc-treated group as the arthritis index and paw swelling had significant reduced（P0.05）.The radiography examination showed that no significant destruction of bony were found while histopathologic analysis displayed relatively synoviocytes hyperplasia and neutrophil infiltration reduction in group treated with rAAV2/rTNFR：Fc.Furthermore,following administration of rAAV2/rTNFR：Fc,serum TNF-α level significant decreased while TNFR level greatly increased（P0.05）.CONCLUSION The results indicate that rAAV2/rTNFR：Fc has anti-arthritic properties in the experimental model.

关 键 词：2型重组腺相关病毒/肿瘤坏死因子受体:IgG1FC融合基因 关节炎 类风湿 基因治疗 胶原性关节炎 

分 类 号：R965[医药卫生—药理学]