关键词: 复方双氯芬酸钠, 骨关节炎, MMP-1, 软骨形态, 氧化应激, 基质金属蛋白酶

Abstract: BACKGROUND: Compound diclofenac sodium is an analgesic and antipyretic, non-steroidal drug, which has been widely used to relieve mild-to-moderate pain and treat rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, and osteoarthritis, musculoskeletal injury. However, there are few reports on its mechanism of action on osteoarthritis.
OBJECTIVE: To explore the effect of compound diclofenac sodium on matrix metalloproteinase 1, cartilage morphology and oxidative stress in osteoarthritis rats. 
METHODS: Rat models of osteoarthritis were established by intra-articular injection of papain and randomly divided into blank group, model group, low, middle-, and high-dose compound diclofenac sodium groups, and celecoxib group. The swelling degree of the right knee joint of rats was measured. ELISA was used to detect the contents of tumor necrosis factor-α, interleukin-1β, and matrix metalloproteinase 1 in the joint effusion. The levels of oxidative stress indicators, superoxide dismutase, malondialdehyde, glutathione peroxidase, were detected. Articular cartilage histology and Mankin score were compared between groups. Western blot was used to detect the protein expression of matrix metalloproteinases 1, 3, and 13 in the articular cartilage. 
RESULTS AND CONCLUSION: After modeling and before administration, compared with the blank group, rats in the model group, low-, middle-, high-dose groups and celecoxib group all had different degrees of redness and swelling in the right knee joint, but no purple-red spots and nodules. After administration, the degree of redness and swelling of the right knee joint of rats in the model group was significantly reduced in the low-, middle-, high-dose groups and celecoxib group compared with the model group (P < 0.05). The levels of tumor necrosis factor-α, interleukin-1β, and matrix metalloproteinase 1 in the joint effusion were significantly higher in the model group than the blank group (P < 0.05), while these levels were significantly reduced after administration of low-, 
middle-, and high-dose compound diclofenac sodium and celecoxib (P < 0.05). Compared with the blank group, the superoxide dismutase and glutathione peroxidase levels were significantly reduced and the malondialdehyde content was significantly increased in the model group (P < 0.05). Compared with the model group, the low-, middle-, and high-dose groups and the celecoxib group showed the significantly increased levels of superoxide dismutase and glutathione peroxidase and the reduced content of malondialdehyde. Moreover, the changes in the high-dose group were the most significant (P < 0.05). The Mankin score of rats was higher in the model group than the blank group (P < 0.05), but were significantly reduced in the low-, middle- and high-dose groups and the celecoxib group, especially in the high-dose group (P < 0.05). The protein expression levels of matrix metalloproteinases 1, 3, and 13 in the articular cartilage were significantly higher in the model group than the blank group (P < 0.05) and were significantly reduced after administration of low-, middle-, and high-dose compound diclofenac sodium and celecoxib (P < 0.05). To conclude, compound diclofenac sodium can improve the cartilage morphology of osteoarthritis rats, reduce oxidative stress damage, and inhibit the expression of matrix metalloproteinase 1 in cartilage tissue, thereby having a therapeutic effect on bones and joints.

Key words: compound diclofenac sodium, osteoarthritis, MMP-1, cartilage morphology, oxidative stress, matrix metalloproteinase