Abstract:

BACKGROUND: Clinical studies have shown that sodium hyaluronate at different molecular weights exhibits therapeutic effects on osteoarthritis.

OBJECTIVE: To investigate the changes in interleukin-1 beta, tumor necrosis factor-alpha, and matrix metalloproteinase-3 in synovial fluid of osteoarthritis rabbits after treatment with different molecular weights of sodium hyaluronate injection.

METHODS: Forty rabbits (purchased from Qinghai Experimental Animal Center, China) were randomly divided into normal, model, macromolecule, and small molecule groups, with 10 rabbits in each group. The control group did not undergo any treatment. Rabbits in the remaining three groups were injected with papain via the right knee joint cavity to establish rabbit models of osteoarthritis. At 7 days after successful modeling, the right knee joint cavity of rabbits in the macromolecule and small molecule groups were injected with 0.3 mL of (1.5-2.5)×10⁶ Da and (0.8-1.5)×10⁶ Da sodium hyaluronate injection. Rabbits in the model group were injected with equal amounts of physiological saline, once a week, for 5 successive weeks. At 7 days after the last injection, the right knee joint cavity was examined by MRI, cartilage tissue was stained with hematoxylin-eosin, the level of inflammatory factors in the washing fluid was determined, and proteoglycan and collagen gene expression was detected. This study was approved by the Medical Ethics Committee of Qinghai Red Cross Hospital, China (No. 201802065).

RESULTS AND CONCLUSION: MR imaging: There were joint effusion and incomplete cartilage surface in the model group. In the macromolecule group, cartilage surface was rough and cartilage layer became thinner compared with the model group. Hematoxyin-eosin staining: Obvious cartilage injury was observed in the model, macromolecule, and small molecule groups, but the injury in the macromolecule, and small molecule groups was milder than that in the model group. The injury in the small molecular group was milder than that in the macromolecule group. Measurement of inflammatory factors: Compared with the control group, the levels of interleukin-1 beta, tumor necrosis factor-alpha and matrix metalloproteinase-3 increased in the model group (P < 0.05). Compared with the model group, the levels of interleukin-1 beta, tumor necrosis factor-alpha and matrix metalloproteinase-3 decreased in the macromolecule and small molecule groups (P < 0.05). The levels of interleukin-1 beta and matrix metalloproteinase-3 in the small molecule group were lower than those in the macromolecule group. There was no significant difference in the level of tumor necrosis factor-alpha between small molecule and macromolecule groups. Gene detection: Proteoglycan and collagen gene expression levels were significantly lower in the model group than in the control, macromolecule and small molecule groups (P < 0.05). Proteoglycan and collagen gene expression levels were significantly lower in the macromolecule group than in the small molecule group (P < 0.05). These results suggest that compared with large molecular weight of sodium hyaluronate, small molecular weight of sodium hyaluronate can promote the repair of cartilage tissue in osteoarthritis and alleviate synovitis inflammation.

Key words:

sodium hyaluronate, different molecular weights, osteoarthritis, interleukin-1beta, tumor necrosis factor-alpha, matrix metalloproteinase-3, articular cavity, cartilage tissue