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

 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：IgG₁F_C 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。

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

OBJECTIVE To investigate the effect of intramuscular rAAV2/rTNFRFc 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/rTNFRFc-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/rTNFRFc -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/rTNFRFc. Furthermore， following administration of rAAV2/rTNFRFc， serum TNF-α level significant decreased while TNFR level greatly increased (P<0.05. CONCLUSION The results indicate that rAAV2/rTNFRFc has anti-arthritic properties in the experimental model.