关键词: 骨关节炎, 软骨损伤, 雷公藤多苷, Nrf2/HO-1信号通路

Abstract: BACKGROUND: Tripterygium glycosides have multiple pharmacological effects, including immunoregulatory and anti-inflammatory properties, and can reduce local inflammatory responses in the joints by regulating immune cell activity and inhibiting the release of inflammatory mediators in the treatment of osteoarthritis. Additionally, tripterygium glycosides can act on signaling pathways related to chondrocyte and extracellular matrix metabolism, reducing chondrocyte apoptosis and promoting extracellular matrix synthesis, thereby slowing the progression of joint cartilage damage. The mechanisms by which tripterygium glycosides promote cartilage repair and delay the progression of osteoarthritis require further clarification.
OBJECTIVE: To investigate the mechanism by which tripterygium glycosides affect the Nrf2/HO-1 signaling pathway during the treatment of knee osteoarthritis in rats, thereby providing scientific evidence for the treatment of knee osteoarthritis.
METHODS: Thirty-six Sprague–Dawley rats were randomly divided into three groups: a control group, a model group, and a tripterygium glycosides group, with 12 rats in each group. The control group underwent knee joint capsule incision and suturing, followed by postoperative intragastric administration of physiological saline. Anterior cruciate ligament transection was performed in the model and tripterygium glycosides groups, and an osteoarthritis model was established after 4 weeks. The rats in these groups were then administered physiological saline or 50 mg/kg tripterygium glycosides, respectively, by gavage once daily for 4 consecutive weeks, after which tissue samples were collected. Hematoxylin and eosin and Safranin O–Fast Green staining were used to observe morphological changes in the knee joint cartilage. Superoxide dismutase activity was measured in rat serum. The protein expression levels of interleukin-1β, interleukin-10, and tumor necrosis factor-α in rat cartilage tissue were detected by Western blot analysis. The relative protein and mRNA expression levels of nuclear factor erythroid 2–related factor 2 and heme oxygenase-1 were detected using immunohistochemistry, Western blotting, and quantitative reverse transcription polymerase chain reaction assays.
RESULTS AND CONCLUSION:  (1) Compared with the model group, cell morphology and tissue structure in the tripterygium glycosides group were more intact, with clear structural outlines and significantly reduced inflammatory cell infiltration. (2) Pathological changes in the knee joint cartilage of rats were significantly alleviated in the tripterygium glycosides group compared with the model group. Safranin O–Fast Green staining was darker and more uniform in the tripterygium glycosides group than in the model group. The number of chondrocytes increased, and their arrangement became more regular. Inflammatory cell infiltration in the synovium was reduced, and the cartilage surface was relatively smooth. (3) Serum superoxide dismutase activity was significantly higher in the tripterygium glycosides group than in the model group (P < 0.01). (4) Immunohistochemical staining showed that the mean absorbance values for nuclear factor erythroid 2–related factor 2 and heme oxygenase-1 immunoreactivities were significantly lower in the model and tripterygium glycosides groups than in the control group (P < 0.01) and significantly higher in the tripterygium glycosides group than in the model group (P < 0.01). (5) Compared with the model group, the expression levels of the inflammatory factors interleukin-1β and tumor necrosis factor-α were significantly reduced in the tripterygium glycosides group (P < 0.01), whereas the expression of the anti-inflammatory factor interleukin-10 was significantly increased (P < 0.01). (6) Compared with the model group, the protein and mRNA expression levels of nuclear factor erythroid 2–related factor 2 and heme oxygenase-1 in rat knee joint tissue were significantly increased in the tripterygium glycosides group (P < 0.01). (7) These findings suggest that tripterygium glycosides can alleviate cartilage damage by decreasing the release of inflammatory factors and activating the nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway, thereby protecting the articular cartilage.

Key words: osteoarthritis, cartilage injury, Tripterygium glycosides, Nrf2/HO-1 signaling pathway