肌肉注射CTLA4-FasL重组腺相关病毒抑制大鼠关节炎的实验研究  

Intramuscular administration of recombinant CTLA4-FasL adeno-associated virus suppresses rat arthritis

作　　者：张晓郡[1,2] 王芳[2] 王博[2] 高燕[2] 于继云[2] 徐元基[2] 阎瑾琦[2] 王宇[2] 张巍[2] 

机构地区：[1]广西医科大学免疫学研究室,南宁530021 [2]军事医学科学院基础医学研究所转化医学研究室,北京100850

出　　处：《免疫学杂志》2012年第10期858-861,876,共5页Immunological Journal

摘　　要：目的观察CTLA4-FasL融合基因能否有效抑制大鼠关节炎。方法在动物造模免疫第2天,以肌肉注射方式导入CTLA4-FasL和EGFP(对照)重组腺相关病毒(rAAV),持续观察和测量2组动物的临床指标包括关节指数、踝关节厚度和体质量等,并对踝关节的组织学表现如滑膜增生和炎性细胞浸润等进行了检测。结果应用大鼠佐剂诱导关节炎动物模型,明确了重组AAV病毒可介导目的基因CTLA4-FasL于体内表达;与rAAV.EGFP对照组相比,rAAV.CTLA4-FasL处理组在临床学和组织学表现上均有效抑制了大鼠关节炎。结论 CTLA4-FasL融合分子很可能是具有潜在研究价值的类风湿性关节炎治疗分子。This study aimed to detect the inhibitory effect of CTLA4-FasL fusion gene on rat arthritis.Recombinant adeno-associated virus（rAAV） vectors encoding rat CTLA4-FasL fusion gene（rAAV·CTLA4-FasL） or enhanced green fluorescent protein（rAAV·EGFP） were injected intramuscularly into rats on the next day of rat arthritis model setup.Continuously,the clinical indexes of two groups,including articular index,ankle joint thickness and weight,were observed and measured.Furthermore,the ankles were monitored by histological changes including synovial hyperplasia,and inflammatory cells infiltration.We found that the recombinant AAV could efficiently mediate the expression of CTLA4-FasL in vivo,and treatment using rAAV·CTLA4-FasL resulted in a significant suppression of rat AIA as reflected in the clinical signs and histological characters comparing with the treatment using rAAV·EGFP.Our results implicate the potential therapeutic applications of CTLA4-FasL for suppression of RA.

关 键 词：重组腺相关病毒 CTLA4-FASL 类风湿性关节炎 动物模型 

分 类 号：R593.22[医药卫生—内科学]