SCID小鼠耳廓皮下滑膜移植模型的建立及其在英夫利昔疗效评估中的应用  

Establishment of SCID-HuRAg model with rheumatic synovium in ear pouch and its application in efficacy evaluation of infliximab

作　　者：贾俊峰[1] 朱平[1] 王聪华[1] 赵金康[1] 贾筠[1] 

机构地区：[1]第四军医大学西京医院临床免疫科,陕西西安710033

出　　处：《第四军医大学学报》2008年第15期1345-1347,共3页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金重点项目(30530720)

摘　　要：目的:建立一种简便、可靠、易于给药及观察的小鼠荷人类风湿关节炎(RA)滑膜模型,为抗RA药物疗效及其机制的体内研究提供实验系统.方法:无菌获取4例RA患者膝关节滑膜组织,修剪成3 mm3大小,移植入严重联合免疫缺陷小鼠(SCID)耳廓皮下,同时以2例OA滑膜作为对照.移植入4 wk后开始,给予TNF-αmAb体英夫利昔治疗4 wk,以无关抗人IgG1抗体作为对照.隔日观察,根据移植物红肿程度对炎症进行评分.移植入8 wk后,处死小鼠取出移植物,进行苏木素-伊红(HE)染色病理分析.结果:人滑膜在SCID小鼠体内存活至少8 wk,移植后RA滑膜炎症大体评分高于OA滑膜组(P<0.05);移植前后RA滑膜病理特点无明显变化,经局部注射TNF-α抗体治疗后炎症评分降低(P<0.05),病理检测示滑膜增殖及淋巴细胞浸润评分降低(P<0.05).结论:SCID-HuRAg模型的病理特点与RA患者体内类似;经局部注射生物靶向药物英夫利昔后有相应改善,是对RA滑膜炎症机制进行体内研究的一种简便实用模型.AIM： To establish a simple and reliable SCID mice model engrafted with rheumatic synovium（SCID-HuRAg） which is easy for drug administration and observation, and to provide an experimental system to study the efficacy and mechanism for antirheumatic drugs in vivo. METHODS： Synovial tissues from 4 human rheumatoid arthritis（RA） and 2 osteoarthritis （OA） patients were trimed and implanted subcutaneously in the ear pouches of 15 SCID mice. SCID-HuRAg mice were treated with chimeric anti-TNF-α monoclonal antibody, infliximab （mAb, 100 microg/ mouse for 4 weeks）. Human immunoglobulin G1 （IgG1） was administered to mice as a control. The degree of synovitis was evaluated by Synovitis Clinical Score. The effects of infliximab on the synovial proliferation, lymphocytes infiltration and neovascularization of RA synovial tissue were examined pathologically by Haematoxylin/eosin staining 4 weeks after the initial administration. RESULTS： RA and OA synovial tissue grew well at least for 8 weeks in subcutaneous ear pouches of the SCID mice and maintained the histologie characteristics of the fresh synovial tissue before implantation. Synovitis clinical score of RA group was much higher than that of OA group （ P 〈 0.05 ）. Pathologcial score for synovial proliferation and lymphocyte infiltration of the RA synovium in the model were reduced after anti-TNF-α monoclonal antibody administration （ P 〈 0. 05 ）. CONCLUSION： Pathology characteristic of SCID mice established by ear pouch engratment resemble that of RA synovium in vivo and can be improved by theanti-rheumatic biologics infliximab, indicating this model is a simple and reliable model for in vivo study of RA synovitis.

关 键 词：关节炎 类风湿 联合免疫缺陷小鼠 模型 动物 滑膜炎 

分 类 号：R593.21[医药卫生—内科学]