Abstract: BACKGROUND: In recent years, there have been new progresses in the treatment of knee osteoarthritis by traditional Chinese medicine in terms of pathogenesis and clinical application. Therefore, Chinese medicines for relaxing tendons and dredging collaterals and replenishing qi and enriching the blood should be used as the treatment standard.
OBJECTIVE: To investigate the effects of Yiqi Huoxue Tongluo Decoction on synovial cells, microstructure, and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 protein of the knee joint in rats with knee osteoarthritis. 
METHODS: A total of 60 healthy rats were selected and randomly divided into healthy group, model group, Chinese medicine low-dose group, Chinese medicine middle-dose group, Chinese medicine high-dose group, and western medicine group. Animal models of knee osteoarthritis were prepared in the latter five groups. At 24 hours after modeling, the rats in the healthy and model groups were intragastrically given normal saline 3 mg/kg per day, while those in the low-, middle-, and high-dose groups were intragastrically given Yiqi Huoxue Tongluo Decoction 3, 6, 9 mg/kg per day, respectively. In the western medicine group, prednisone was intragastrically administered, 5 mg/kg per day. After 4-week intervention, bone microstructure was detected. TUNEL was used to detect the apoptotic rate of synovial cells. Hematoxylin-eosin staining was used to observe the pathological morphology. Western blot and PCR were used to detect the expressions of ADAMTS-5, matrix metalloproteinase 1, and matrix metalloproteinase 3 in rat bone joints, respectively.
RESULTS AND CONCLUSION: Compared with the healthy group, the number of trabecular bone, trabecular bone thickness, bone volume fraction, and bone mineral density of the knee joint were decreased, while structural model index, trabecular bone separation degree, and expression of ADAMTS-5, matrix metalloproteinase 1, and matrix metalloproteinase 3 mRNA and protein in the knee joint of rats were significantly increased in the model group (P < 0.05). The low-dose group shared similar effects with the model group (P > 0.05). Compared with the model group, the number of trabecular bone, trabecular bone thickness, bone volume fraction, and apoptotic rate of synovial cells were increased in the middle-dose group, while structural model index, trabecular bone separation degree, and expression of ADAMTS-5, matrix metalloproteinase 1, and matrix metalloproteinase 3 mRNA and protein in the knee joint were significantly decreased (P < 0.05). The middle-dose group shared similar effects with the western medicine group (P > 0.05). Compared with the middle-dose group, the above-mentioned indicators were all improved in the high-dose group (P < 0.05). In the model and low-dose groups, bone cells of the knee joint were severely damaged and a large number of inflammatory cells were observed. There was still chondrocyte destruction and inflammatory cell infiltration on the bone surface of knee joint in the middle-dose group and the western medicine group. In the high-dose group, a small number of inflammatory cells gathered and the knee surface bone tended to be smooth. All these findings indicate that Yiqi Huoxue Tongluo Decoction has a therapeutic effect on knee osteoarthritis rats, and the high-dose group has the most significant effect. Its mechanism may be related to the improvement of bone microstructure and regulation of synovial cell activity and ADAMTS-5 expression.

Key words: Yiqi Huoxue Tongluo Decoction, knee osteoarthritis, synovial cells of the joint, bone microstructure, ADAMTS-5, apoptosis, rat