Influence of resveratrol on apoptosis in knee osteoarthritis rats by regulating autophagy mediated by SIRT1/AMPK signaling pathway
Objective:To investigate the effect of resveratrol on apoptosis of chondrocytes in rats with knee osteoarthritis(KOA)through autophagy mediated by silent information regulator 1(SIRT1)/adenylate activated protein kinase(AMPK)signaling pathway.Methods:Fifty healthy Wistar rats were randomly separated into control group,model group,resveratrol group,resveratrol+ SIRT1 inhibitor group,and autophagy activator group,with 10 rats per group.Except for the control group,the other rats were injected with Freund's complete adjuvant to establish the KOA rat model,resveratrol group,resveratrol+AMPK inhibitor group,and autophagy activator group were treated with 10 µmol/kg resveratrol,10 µmol/kg resveratrol+10 mg/kg EX527,2 mg/kg rapamycin,respectively.After 4 weeks,the grade of Lequesne MG knee joint of rats were observed;the levels of IL-6 and tumor necrosis factor-β(TNF-β)in rat knee joint fluid were measured;HE staining and TUNEL staining were used to observe the morphology and apoptosis of rat knee cartilage;transmission electron microscope was used to observe the autophagy in rat chondrocytes;Western blot was performed to determine the protein expressions of SIRT1,p-AMPK,AMPK,LC3 and Beclin-1.Results:Compared with control group,the local reaction,gait reaction,joint activity,and joint swelling of model group were increased;compared with model group,the local response,gait response(P<0.05),joint activity,and joint swelling in resveratrol group and autophagy activator group were reduced(P<0.05).Compared with control group,the cartilage tissue cells in model group were disordered and rough,with fibrotic degeneration,marginal humeral bulge,reduced organelles,and vacuolar degeneration,the number of autophagosomes was increased,the levels of IL-6 and TNF-β in knee joint fluid,chondrocyte apoptosis rate,Beclin-1 and LC3B/A were increased(P<0.05),the SIRT1 and p-AMPK/AMPK in cartilage tissue were decreased(P<0.05);compared with model group,resveratrol group and autophagy activator group showed improvement in the disordered arrangement of cartilage tissue cells and the marginal humeral bulge,the number of autophago-somes was increased,the levels of IL-6 and TNF-β in knee joint fluid,and the apoptosis rate of chondrocytes were decreased(P<0.05),the levels of SIRT1,p-AMPK/AMPK,Beclin-1 and LC3B/A in cartilage tissue were increased(P<0.05);SIRT1 inhibitor could reverse the protective effect of resveratrol group on rat chondrocytes.Conclusion:Resveratrol maybe autophagic KOA rat chon-drocyte apoptosis mediated by activating SIRT1/AMPK pathway,which can be reversed by SIRT1 inhibitor.
Knee osteoarthritisResveratrolAutophagySilent information regulator 1/adenylate activated protein kinase
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