Role and underlying mechanism of resveratrol in trimethylamine N-oxide-induced vascular aging in mice
KE Yilang
ZHOU Yuanyuan
PAN Fuxiang
LI Dang
HONG Huashan
Abstract：Objective To investigate the role and underlying mechanism of resveratrol(RSV)in trimethylamine N-oxide(TMAO)-induced vascular aging in senescence-accelerated mouse prone 8(SAMP8)mice.Methods A total of 36 male SAMP8 mice(24 weeks old)were randomly divided into control,TMAO,and TMAO+RSV groups,with 12 mice per group.The control group received drinking water and intragastric administration of RSV vehicle,0.5％sodium carboxymethyl cellulose(NaCMC).The TMAO group received drinking water containing 1.5％ TMAO and intragastric administration of NaCMC.The TMAO+RSV group received 1.5％ TMAO in drinking water and intragastric administration of 50 mg/kg RSV.After 16 weeks of intervention,pulse wave velocity(PWV)and maximum endothelium-dependent relaxation(Emax)were measured,aortic structure and senescence-associated β-galactosidase(SA-β-gal)were observed,and the protein expression levels of P53,P21,silent mating type information regulation 2 homolog-1(SIRT1),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),and superoxide dismutase 2(SOD2)were detected.Results Compared with the control group,the TMAO group exhibited significantly larger aortic lumen diameter,thicker wall thickness,increased wall area,more elastic fiber breaks,enhanced SA-β-gal positive area,and higher PWV and protein levels of P53 and P21,whereas obviously decreased Emax and expression levels of SIRT1,PGC-1α,and SOD2(P＜0.05).RSV treatment resulted in significant decreases in aortic lumen diameter,wall thickness,wall area,elastic fiber breaks,PWV and protein levels of P53 and P21 in the aorta,and increases in Emax and expression levels of SIRT1,PGC-1α and SOD2[(47.43±7.27)％vs(29.48±4.28)％,0.43±0.18 vs 0.18±0.14,0.80±0.26 vs 0.22±0.08,1.22±0.41 vs 0.25±0.07,P＜0.05].Conclusion RSV can ameliorate TMAO-accelerated vascular aging in SAMP8 mice,potentially through activation of the SIRT1/PGC-1α/SOD2 pathway.
Keywords：resveratrolagingsirtuin 1superoxide dismutase
Publication Date：2026-03-15
Online Publishing Date：2026-03-31(First online date of this platform, not the publication date of the document)
Pages：5( 301-305 )