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.

Objective To establish an animal model of rheumatoid arthritis(RA) and isolate fibroblast-like synoviocytes(FLS) from inflammatory synovium.Methods Modified adjuvant was prepared using heat-killed Mycobacterium tuberculosis H37Ra with sterile mineral oil,and arthritis was induced in Lewis rats by injection of the adjuvant at base of tail.Synovial tissue specimens were taken from arthritic ankle joints followed by mincing adequately.FLS were isolated by collagenase digestion.Results Arthritis was successfully induced in the rats.The incidence reached 100% with regular time of arthritis development,and the histological changls were similar to those of rheumatoid arthritis.FLS were successfully obtained,identified and characterized in vitro.Conclusions An animal model of RA has been successfully established in rats and FLS have been successfully obtained,providing a desirable in vivo animal model and in vitro cell model for exploration of RA pathogenesis and drug evaluation.