The rat osteoarthritis model was replicated by injection of sodium iodoacetate into the knee joint cavity, and the effects of Gancao Fuzi Decoction on rat osteoarthritis and the proteome of articular cartilage were investigated. Sixty SD rats weighing 230-250 g were randomly divided into normal group, model group, glucosamine sulfate group, and Gancao Fuzi Decoction high, medium and low dose groups. Osteoarthritis model was induced by intra-articular injection of sodium iodoacetate(3 mg on each leg) in all groups except the normal group. After modeling, each administration group was given intragastric administration for 1 month. During the administration period, joint pain test and joint width measurement were performed every week to observe the autonomous behavior of rats. Enzyme linked immunosorbent assay(ELISA) method was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase tissue inhibitor(TIMP-1) in rat joint lavage fluid. Hematoxylin-eosin(HE) staining was used to observe bone and joint morphology. Nano-LC-LTQ-Orbitrap system was used to detect arti-cular cartilage proteins. The results showed that, compared with the model group, Gancao Fuzi Decoction could significantly improve joint pain and joint swelling in osteoarthritis rats, significantly reduce the contents of TNF-α, IL-1β and MMP-3 in the joint cavity la-vage fluid, increase the content of TIMP-1, and relieve inflammatory diseases such as enlarged joint space, rough cartilage edge, different thickness of cartilage layer, and disordered arrangement of chondrocytes. After comparing the proteins between the groups, 273 differential proteins were screened out. KEGG analysis found that the above differential proteins involved 43 signaling pathways such as systemic lupus erythematosus, among which 11 signaling pathways were related to osteoarthritis. The above results indicated that Gancao Fuzi Decoction had a preventive effect on osteoarthritis, and its mechanism of action may be accomplished by regulating the protein expression of osteoarthritis-related signal pathways.

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