黄豆苷元对膝骨关节炎大鼠软骨细胞凋亡及SIRT1/AMPK信号通路的影响OA

Objective:To investigate the effects of daidzein(DZ)on chondrocyte apoptosis and the silent information regulator 1(SIRT1)/AMP-activated protein kinase(AMPK)pathway in knee osteoarthritis(KOA)rats.Methods:SD rats were divided into six groups:control group,model group,low-dose DZ group(5 mg/kg),medium-dose DZ group(10 mg/kg),DZ high-dose group(20 mg/kg)and positive control group(0.017 g/kg Viartril-S).An adjuvant-induced KOA rat model was established in all groups except the control group.After successful modeling,the rats were treated with the corresponding medications.H-E staining was performed to measure the pathological changes of cartilage tissue in KOA rats;ELISA was adopted to observe the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in cartilage tissue of KOA rats.TUNEL staining was applied to detect chondrocyte apoptosis;immunohistochemistry was used to determine the expressions of SIRT1 and p-AMPK in cartilage.CCK-8 assay was utilized to assess the proliferation of chondrocytes;flow cytometry was employed to measure apoptosis of chondrocyte.Western blotting analysis was conducted to evaluate the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),SIRT1 and p-AMPK in chondrocytes.Results:Low,medium and high doses of DZ or Viartril-S alleviated the pathological injury of rat cartilage tissue,reduced the percentage of TUNEL-positive cells,the levels of IL-1β,TNF-α,apoptosis rate,and Bax protein expression,and improved the rate of SIRT1 and p-AMPK positive cells,the proliferation ability of chondrocytes,and the protein expression of Bcl-2,SIRT1 and p-AMPK.Conclusion:DZ can inhibit the apoptosis of chondrocytes in KOA rats,and the mechanism may be related to the activation of the SIRT1/AMPK pathway.