Mechanism of Taohong Siwu Decoction(桃红四物汤)in Regulating Ferroptosis Mediated by Nrf2/Keap1/HO-1 Signaling Pathway in Knee Osteoarthritis
Objective:To investigate the mechanism of Taohong Siwu Decoction(桃红四物汤)in regulating the Nrf2/Keap1/HO-1 signaling path-way-mediated ferroptosis in knee osteoarthritis(KOA).Methods:40 SD rats were randomly divided into a sham surgery group,a model con-trol group,Taohong Siwu Decoction(9 g/kg)group,and a diacerein capsule(0.0045 g/kg)group,with 10 rats in each group.Rat models were established by using medial meniscus instability surgery.After successful modeling for one week,rats were given corresponding medica-tion or the same dose of sterile water by gavage,once a day for eight weeks.After the intervention was completed,the levels of serum interleu-kin-1β(IL-1β),tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),as well as the levels of malondialdehyde(MDA),superoxide dis-mutase(SOD),and reactive oxygen species(ROS)in articular cartilage tissue were detected.The number,morphology,structure,and distri-bution of cartilage mitochondria in each group were observed by transmission electron microscopy.Western blot was used to detect the expres-sion of Keap1,Nrf2,HO-1,glutathione peroxidase 4(GPX4),tumor suppressor protein 53(P53),and solute carrier family 7 member 11 re-combinant protein(SLC7A11)in rat articular cartilage.Results:Compared with the sham surgery group,the pathological scores of Mankin and OARSI in the model control group were increased,the levels of IL-1β,TNF-α,IL-18,MDA,and ROS were significantly increased,and the protein expressions of Keap1 and P53 were significantly up-regulated.The SOD activity was significantly decreased,and the protein expres-sions of Nrf2,HO-1,GPX4,and SLC7A11 were significantly down-regulated(P＜0.01).Compared with the model control group,the patho-logical scores of Mankin and OARSI in the Taohong Siwu Decoction group were decreased,and the levels of IL-1β,TNF-α,IL-18,MDA,and ROS were decreased.The protein expressions of Keap1 and P53 were significantly down-regulated.The SOD activity was increased,and the protein expressions of Nrf2,HO-1,GPX4,and SLC7A11 were significantly up-regulated(P＜0.01).Conclusion:Taohong Siwu Decoction may inhibit ferroptosis in rat articular cartilage by activating the Nrf2/Keap1/HO-1 signaling pathway.
万方数据
维普
