腺病毒介导核因子κBp65特异性小干涉RNA抑制骨关节炎  

Osteoarthritis suppression by delivery of the adenoviral vector-mediated nuclear factor kappa Bp65-specific small interfering RNA

作　　者：陈连旭[1] 于长隆[1] 

机构地区：[1]北京大学第三医院运动医学研究所,北京市100191

出　　处：《中国组织工程研究》2012年第46期8551-8555,共5页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(30671017)~~

摘　　要：背景:前期系列研究表明,核因子κBp65特异性小干涉RNA重组腺病毒可以在SD大鼠膝关节软骨和滑膜内抑制核因子κBp65的表达,降低核因子κB的转录活性,抑制关节内白细胞介素1β和肿瘤坏死因子α的表达。目的:在大鼠关节内观察腺病毒介导的核因子κBp65特异性小干涉RNA对骨关节炎的抑制作用。方法:将3月龄雄性近交系SD大鼠分为4组,正常关节组只切开皮肤及关节腔后立即缝合切口。其余大鼠切断膝关节内侧副韧带,切除部分内侧半月板,诱导大鼠关节的骨关节炎。骨关节炎组造模后未作任何处理;空病毒注射组造模后两侧膝关节关节腔注射腺病毒空载体0.2mL;特异性小干涉RNA注射组造模后两侧膝关节关节腔注射携带核因子κBp65特异性小干涉RNA重组腺病毒0.2mL。结果与结论:与正常关节软骨相比,骨关节炎组和空病毒注射组关节软骨组织评分及滑膜组织评分显著增高(P<0.01),特异性小干涉RNA注射组组织评分明显减低(P<0.01),但未到正常关节软骨和滑膜水平(P<0.01)。提示腺病毒介导的核因子κBp65特异性小干涉RNA可以抑制骨关节炎的发展。BACKGROUND：Preliminary studies have demonstrated that recombinant adenovirus expressing nuclear factor κBp65（NF-κBp65） specific small interfering RNA（siRNA） can suppress NF-κBp65 expression in the knee cartilage and synovium,decrease transcriptional activity of NF-κB and limit the levels of interleukin 1β and tumor necrosis factor α.OBJECTIVE：To observe the effect of adenoviral vector-mediated NF-κBp65-specific siRNA on experimental osteoarthritis in the rat knee.METHODS：Three-month aged male Sprague-Dawley rats were divided into four groups.The osteoarthritis model was induced by transection of the medial collateral ligament and partial medial meniscectomy in the rat knee.Then,0.2 mL adenoviral vector-mediated NF-κBp65-specific siRNA and adenovirus were injected into the knee of NF-κBp65-specific siRNA and adenovirus groups,respectively.There was no treatment in the osteoarthritis group,no modeling in the normal group.RESULTS AND CONCLUSION：The scores on the knee cartilage and synovium were significantly increased in the osteoarthritis and adenovirus groups（P0.01）,while the scores in the NF-κBp65-specific siRNA group were decreased dramatically（P0.01）,but still higher as compared with the normal group（P0.01）.Adenoviral vector-mediated NF-κBp65-specific siRNA can suppress the progression of early experimental osteoarthritis.

关 键 词：核因子ΚBP65 小干涉RNA 腺病毒 骨关节炎 关节软骨 滑膜 膝关节 大鼠 组织构建 

分 类 号：R318[医药卫生—生物医学工程]