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. [ABSTRACT FROM AUTHOR]