Study of the Duhuo Jisheng Decoction in Delaying Cartilage Degeneration of Knee Osteoarthritis in Rats by Regulating the Chondrocyte Ferroptosis Activation Effect
Objective:To observe the protective effect of Duhuo Jisheng decoction on chondrocytes of surgically induced knee osteoarthritis(KOA)model rats and to explore its relationship with ferroptosis of chondrocytes.Methods:40 female SD rats with SPF grade were randomly divided into blank group,model group,experimental group and control group,with 10 rats in each group.Except for the blank group,the modified Hulth method was used to prepare the KOA model;the blank group opened the joint cavity without any treatment in the same way,and sutured the joint cavity after surgery.The experimental group received gavage of the traditional Chinese medicine Duhuo Jisheng decoction at a rate of 9.3 g/(kg·d),commencing from 4 weeks after the operation.The blank group and model group were both administered saline gavage at an equal amount,whereas the control group was given 2 mg/(kg·d)injection of the Ferrostatin-1 iron death inhibitor into the joint cavity for a duration of 12 weeks.Hematoxylin and eosin(HE)staining was utilized to observe the morphology of knee joint cartilage tissues of rats in each group.Mankin scoring system was utilized for quantitative assessment.Additionally,levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH)in the serum of rats in each group were determined using colorimetric assay.The levels of upstream signaling inhibitor(P53),solvent inhibitor,and oncogene(P53)in the cartilage tissues of the knee joints were analyzed by Western Blot in each group of rats.The protein expression of P53,solute carrier family 7 member 11(SLC7A11),glutathione per-oxidase 4(GPX4)and matrix metalloproteinase 13(MMP-13)in the same cartilage tissues was also detected using West-ern Blot.Results:Compared with the blank group,rats in the model group presented conspicuous pathological injury to their knee cartilage,and had a higher Mankin score,an elevated serum MDA level(P＜0.05),reduced SOD and GSH lev-els(P＜0.05),raised P53 and MMP-13 proteins in their cartilage tissue(P＜0.05),and decreased SLC7A11 and GPX4 proteins(P＜0.05).Compared with the model group,the pathological damage of knee cartilage in experimental group and control group was improved,the Mankin score was decreased;the contents of MDA in serum were decreased(P＜0.05);the contents of SOD and GSH were increased(P＜0.05);the proteins of P53 and MMP-13 in cartilage were decreased(P＜0.05),and the proteins of SLC7A11 and GPX4 were increased(P＜0.05).Conclusion:Duhuo Jisheng decoction can protect the cartilage of KOA model rats by regulating the ferroptosis of chondrocytes.The mechanism may be to inhibit the ferroptosis of chondrocytes by regulating the P53/SLC7A11/GPX4 signaling pathway,thus delaying the cartilage degeneration of KOA.
Duhuo Jisheng decoctionosteoarthritisoxidative stressiron death
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