类风湿关节炎滑膜侵蚀软骨SCID鼠模型的建立及初步实验研究  

The pathogenesis of cartilage erosion of rheumatoid arthritis and the development of animal model by engraftment of RA synovium and normal human cartilage under the kidney capsule of the SCID mice

作　　者：史战国[1] 朱平[1] 贾俊峰[1] 卢宁[1] 赵金康[1] 李鸿明[1] 王彦宏[1] 樊春梅[1] 肖李冰 

机构地区：[1]第四军医大学西京医院临床免疫科,西安710032 [2]西安市第五医院骨与关节炎科

出　　处：《中华风湿病学杂志》2006年第8期466-469,i0001,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金重点资助项目(30530720)

摘　　要：目的建立类风湿关节炎(RA)-SCID小鼠模型,观察滑膜对软骨的侵蚀情况,为探讨RA滑膜侵蚀软骨机制及治疗奠定基础。方法70只SCID小鼠,3～6周龄。无菌获得12例非关节炎患者正常关节软骨,修剪成约2 mm×2 mm×1 mm后备用。同时取10例RA患者(膝关节或髋关节)滑膜组织修剪成约3 mm×6 mm的小块(片),这些小块包裹软骨后共植入SCID鼠肾包囊处,4例骨关节炎(OA)患者滑膜及2例正常滑膜同样处理作对照。术后观察小鼠和移植物的一般情况,从第4周开始分批处死SCID小鼠并切除移植物,进行苏木素-伊红(HE)染色病理分析。结果大部分滑膜及软骨在SCID小鼠体内存活,4周开始滑膜黏附并侵蚀软骨,12周后RA滑膜明显破坏软骨,移植物细胞浸润、软骨破坏与RA病理类似,OA滑膜轻微破坏软骨,而正常滑膜几乎不破坏软骨。结论RA滑膜植入SCID可成活并能侵蚀软骨,RA-SCID小鼠可作为人源化滑膜侵蚀软骨模型,在探讨机制特别是软骨破坏及治疗方面可能有明显优势。Objective To develop the humanized animal model for RA cartilage erosion, and study the mechanisms of its pathogenesis. Methods RA synovium and normal human cartilage under the kidney capsule of the SCID mice were engrafted, and were maintained for 4～16 weeks. In addition, mice underwent similar surgery except the engraftment served as controls. After 4, 8, 12 or 16 weeks, the mice were killed and the grafts were harvested and the cartilage destruction was assessed histologically by haematoxylin/eosin-stained paraffin sections. Results Histological examination revealed the presence of infiltration of RA synovium cells into the cartilage after 4 weeks and the cartilage was destructed evidently. These studies demonstrated that the RA-SCID model maintained many of the phenotypic and functional features of RA. Conclusion This RA-SCID mouse is a useful animal model for study of the pathogenesis and the development of new drugs for RA patients.

关 键 词：模型 动物 关节炎 类风湿 滑膜 软骨 SCID鼠 

分 类 号：R593.22[医药卫生—内科学]