AdipoRon delays renal aging induced by D-gal in mice via activating the SIRT1 signaling pathway
Objective To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods Male C57BL/6J mice were randomly divided into three groups:a control group,a D-gal model group,and an AdipoRon group,each consisting of ten mice.The control group received saline through gavage and subcutaneous injection,the D-gal group received saline through gavage and D-gal through subcutaneous injection,and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks,following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining,Masson staining,and electron microscopy.Levels of serum creatinine(SCr),urea nitrogen(BUN),and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53,P21,P16INK4a,Silent mating-type information regulation 2 homolog 1(SIRT1),Nuclear factor E2-related factor 2(NRF2),and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results The glomeruli exhibited sparse and irregular structure,with sclerosis and dilated capsular space.Renal tubules showed atrophy,while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 µmol/L),BUN(19.58±1.63 μmol/L),and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely,SCr(16.97±1.16 μmol/L),BUN(16.25±1.25 μmol/L),and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group(F=66.61,40.37,48.77,all P＜0.001).The expression levels of aging proteins like P53(1.68±0.11),P21(2.40±0.45),and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast,anti-aging proteins such as SIRT1(0.46±0.04),NRF2(0.65±0.05),and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06),P21(1.84±0.35),and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely,the expression levels of anti-aging proteins such as SIRT1(0.78±0.05),NRF2(0.87±0.07),and Klotho(0.65±0.06)were increased compared to the D-gal group(F=152.38,44.45,147.54,219.69,42.25,166.49,all P＜0.001).Conclusions AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.
万方数据
维普
