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。
Abstract
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 (P<0.05. 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 (P<0.05. 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
{{custom_keyword}} /
Key words
rAAV/TNFR：FC /
rheumatoid arthritis /
gene therapy /
collagen induced arthritis
{{custom_keyword}} /
周晓冰 高凯 沈连忠 赵爱志 康禹 王刚 吴小兵 王军志 李波.
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[J]. 中国药学杂志, 2011, 46(7): 507-511
ZHOU Xio-ing;GO Ki;SHEN Lin-zhong;ZHO i-zhi;KNG Yu;WNG Gng;WU Xio-ing;WNG Jun-zhi;LI o.
Anti-Inflammatory Effect of Intramuscular rAAV2/rTNFR：Fc Gene Transfer on Collagen Induced Arthritis in Rats[J]. Chinese Pharmaceutical Journal, 2011, 46(7): 507-511
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] PENG X. Development in diagnosis and treatment of rheumatoial arthritis[J].New Chin Med （新医学，2002，33(1： 4-5.
[2] HANG H G， WANG Y M， XIE J F， et al. Regulation of tumor necrosis factor mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt[J]. Arhtritis Rheum， 2001， 44 (7：1555-1567.
[3] TOUSSIROT E， WENDLING D. The use of TNF-alpha blocking agents in rheumatoid arthritis： an overview[J]. Expert Opin Pharmacother， 2004， 5(3： 581-594.
[4] BLOQUEL C， BESSIS N， BOISSIER M C， et al. Gene therapy of collagen-induced arthritis by electrotransfer of human tumor necrosis factor-alpha soluble receptor I variants[J]. Hum Gene Ther， 2004， 15(2：189-201.
[5] PATRICK M， KURT V， TANIA M，et al. Enhanced autoimmune arthritis in IFN-γ receptor-deficient mice Is conditioned by mycobacteria in freund′s adjuvant and by increased expansion of Mac-1+ myeloid cells[J]. J Immunol， 1999， 163 (6：3503-3510.
[6] TANG W L. Detelopment of type Ⅱ collagen induced arthritis model[J]. Chin Pharmacol Bull（中国药理学通报， 1998， 14(6： 495-498.
[7] HOLMDAHL R， BOCKERMANN R， BCKLUND J， et al. The molecular pathogenesis of collagen-induced arthritis in mice--a model for rheumatoid arthritis[J]. Ageing Res Rev， 2002， 1(1：135-147.
[8] FELDMANN M， MAINI S R. Role of cytokines in rheumatoid arthritis[J]. Immunol Rev， 2008， 223(1：17-19.
[9] CARTERON N L. Cytokines in rheumatoid arthritis： Trials and tribulations[J]. Mol Med Today， 2000， 6(8： 315-323.
[10] WEAVER A L. The impact of new biologicals in the treatment of rheumatoid arthritis [J]. Rheumatology， 2004， 43(suppl 3：17-23.
[11] CHAN J M K， VILLARREAL G， JIN W W， et al. Intraarticular gene transfer of TNFR：Fc suppressed experimental arthritis with reduced systemic distribution of the gene product[J]. Mol Ther， 2002， 6(6：727-736.
[12] SEON H K， CHRISTOPHER H E， SUNYOUNG K， et al. Gene therapy for established murine collagen-induced arthritis by local and systemic adenovirus-mediated delivery of interleukin-4[J]. Arthritis Res， 2000， 2(4：293-302.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1279 KB)
