中文摘要：

目的探讨携带人护骨素（hOPG）的重组腺相关病毒（rAAV—hOPG）对胶原诱导性关节炎（CIA）大鼠关节破坏的影响。方法经牛Ⅱ型胶原诱导建立大鼠关节炎模型，随机分成3组：CIA空白对照组，增强绿色荧光蛋白（EGFP）阴性对照组，OPG治疗组，同时设立健康对照组，共4组，每组10只，于首次免疫后第25天开始，分别予磷酸盐缓冲液（PBS）、PBS、rAAV—EGFP、rAAV—hOPG双膝关节腔内注射50μl/侧。比较4组大鼠掌跖厚度、关节炎指数、病理评分、放射学评分、骨破坏因子及炎症因子蛋白表达情况。结果冰冻切片证实AAV能有效转导关节滑膜组织。酶联免疫吸附试验（ELISA）法测得OPG蛋白的表达水平升高93％（P〈0．05），基质金属蛋白酶（MMP）-3蛋白表达下降35％（P〈O．05），而自细胞介素（IL）-1B造模组间比较差异无统计学意义，放射学骨破坏Larsen评分下降30％。结论rAAV～hOPG能有效转导关节组织，表达OPG蛋白，显著减轻炎性关节炎的骨质破坏，可能对关节软骨有一定保护作用，对关节炎症无明显影响。

英文摘要：

Objective Using an in vivo adeno-assoeiated vin, s （AAV）-mediated gene lransfer technique, this study was designed to evaluate the protective effects of human osteoprotegerin （OPG） transgene against joint destruction in collagen induced arthritis （CIA） model. Methods After CIA was established in ＇the Sprague-Dawley rats, the experimental animals were treated with PBS or rAAV-EGFP or rAAV-hOP（; （100 μl/d） intra-artieular injection 25 days after arthritis induction for 10 days. Paraftiu-emhedded joints were then analyzed histologically. The joint destruction was evaluated by Larsen Score. The protein expression of OPG, IL-1, MMP-3 was identified by enzyme-linked immnnnsorbent assay （ELISA）. Results Successful trans-gene expression was confirmed by the detection of OPG by EL1SA and positive fluorescence of the frozen joint section. Image analysis revealed that the expression of OPG significantly protected against joint destruction by 30% compared with the CIA group. Conclusion OPG gene transfer mediated by rAAV effectively protects against bone destruction induced by CIA model. Those data suggest that gene transferring using rAAV-OPG may be a feasible and effective therapeutic approach to treat or prevent joint destruction in inflammatory arthritis.