Abstract:Objective: To investigate the effect of triptolide (TPL) on inflammatory response of acute gouty arthritis (AGA) rats by adjusting TXNIP/NLRP3 pathway. Methods: SD rats were assigned into sham surgery group (Sham), AGA group, AGA+TPL group, AGA+TPL+Ad-NC group, and AGA+TPL+Ad-TXNIP group, each with 12 rats. The degree of ankle joint swelling was measured before modeling and at 4 hours, 8 hours, 24 hours and 48 hours of modeling. Reactive oxygen species (ROS) and superoxide dismutase (SOD) activity detection kits were used to measure ROS and SOD activities. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin (IL)-1β and IL-18 in ankle joint tissue. Hematoxylin-eosin (HE) staining was used to observe the ankle joint tissues. Immunohistochemical staining was used to observe TXNIP in ankle joint tissues. Western blot experiments were used to test TXNIP/NLRP3 pathway related proteins. Results: For the Sham group, the AGA group showed clearly increased swelling degree of ankle joint at each time point, ROS, IL-1β, IL-18, TXNIP, NLRP3, and Caspase 1 (P<0.05), and clearly decreased SOD activity (P<0.05) in rats, the synovial tissue was clearly thickened, inflammatory cells were increased, chondrocytes were noticeably swollen, and joint swelling occurred. For the AGA group, the AGA+TPL group showed clearly decreased swelling degree of ankle joint at 8, 24, and 48 hours after modeling, ROS, IL-1β, IL-18, TXNIP, NLRP3, and Caspase 1 (P<0.05), and clearly increased SOD activity (P<0.05) in rats, the thickness of inflammatory cells and synovial tissue decreased, and inflammation and edema were alleviated. For the AGA+TPS+Ad-NC group, the AGA+TPS+Ad-TXNIP group showed clearly increased swelling degree of ankle joint at 8, 24, and 48 hours after modeling, ROS, IL-1β, IL-18, TXNIP, NLRP3, and Caspase 1 (P<0.05), and clearly decreased SOD activity (P<0.05) in rats, the inflammatory cells and synovial tissue thickness increased, but severe inflammation and edema still occurred in the joints. Conclusion: TPL may alleviate ankle joint injury in AGA rats by adjusting key proteins in TXNIP/NLRP3 pathway, reducing inflammatory response and oxidative stress.
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