Transfection of double gene co-expressing adenovirus vector into arthritis rats
10.3969/j.issn.2095-4344.2015.18.007
- VernacularTitle:构建双基因共表达腺病毒载体转染关节炎模型大鼠的意义
- Author:
Ping FAN
;
Lan HE
;
Zhiming HAO
;
Dan PU
;
Xiaohong LV
;
Yining SUN
;
Nan HU
;
Yanhua WANG
;
Xiaoming DING
;
Yang LI
;
Wujun XUE
- Publication Type:Journal Article
- Keywords:
Arthritis;
Adenoviridae Infections;
Lymphocytes;
T-Lymphocytes
- From:
Chinese Journal of Tissue Engineering Research
2015;(18):2825-2830
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Abnormal activation of lymphocytes and nuclear factorκB-dependent non-specific inflammation are two major manifestations of joint damage in rheumatoid arthritis. Co-stimulatory signal CD40/CD40L is the dominant co-stimulatory factor in the recognition and activation of T cel s. IκBαeffectively inhibits nuclear factorκB pathway, prevent the inflammation in the central link, and suppress the damage caused by inflammatory factor in the synovial tissue.
OBJECTIVE:To investigate the therapeutic effect of double gene co-expressing adenovirus vector on arthritis based on an arthritis model rat transfected by CD40LIg-IRES2-IκBαco-expressing adenovirus vector.
METHODS:The pAdCD40LIg-IRES2-IκBαco-expressing adenovirus vector was established. Arthritic model was established through multi-subcutaneous injections of complete Freund's adjuvant of type col agen II (1 g/L) into Wistar rats. Then 20 arthritic rats were divided into two groups:untreated group and transfection group, receiving an injection of saline and pAdCD40LIg-IRES2-IκBαadenovirus vector to distal joint cavity of limbs, respectively.
RESULTS AND CONCLUSION:At 14 days post-transfection, compared with the untreated group, the mean arthritis index score, the CD40L expression of lymphocytes in synovial fluid, the nuclear factor-κB p65 expression in synovial tissue, and levels of interleukin-2, interleukin-6, tumor necrosis factor-α, matrix metal oproteinase-3 and matrix metal oproteinase-9 in synovial fluid of rats in transfection group were significantly lower than those in untreated group. Focal transfection of the CD40LIg-IκBαco-expression adenovirus vector can effectively inhibit arthritic symptoms, and reduce the expressions of inflammatory cytokine in synovial fluid and inflammatory molecule in synovial tissue of arthritic rats, which shows good therapeutic effect.