Effectof Yishen-Qingluo-Huoxue prescription on OPG/RANKL pathway in CFA rats and its mechanism / 中国药理学通报

ABSTRACT

To investigate the effect of Xinan Fang Yisheng-Qingluo-Huoxie prescription(YSF)on OPG/RANKL pathway in rats with rheumatoid arthritis induced by complete Freund's adjuvant(CFA)and its mechanism. Methods Thirty-two male SD rats were randomly divided into normal group, AIA group, QLY group and YSF group, with 8 rats in each group. AIA rats were induced except for the normal group. QLY and YSF were administered intragastrically on the first day after the model was successful for 30 days. The body weight and AI score of rats were observed. HE staining was used to observe the histomorphological changes of the ankle joint of rats. The expression of MMP3 and P-P65 was observed by immunohistochemistry. Serum levels of TNF-α, IL-1β, OPG and RANKL were detected by ELISA. The expression of OPG and RANKL proteins in synovium of rats was detected by Western blot and RT-PCR. Results Compared with AIA model, the body weight of the rats gradually returned to normal, and inflammation score decreased. HE staining showed that the bone was well preserved, no synovial infiltration was observed after YSF administration, and MMP3 and P-P65 showed low expression. The levels of TNF-α, IL-1β and RANKL in serum were significantly down-regulated, while the levels of OPG and OPG/RANKL were significantly up-regulated. In addition, Western blot and RT-PCR showed that OPG and OPG/RANKL were highly expressed in synovium of rats, while RANKL was on the contrary. Conclusions YSF may decrease inflammatory score and expression of TNF-α and IL-1β in serum by inhibiting inflammatory response. What's more, the increase of OPG/RANKL ratio can regulate the environment of joint bone destruction, thus alleviating RA.