白藜芦醇通过调控SIRT1/p21通路抑制内皮细胞衰老从而抑制腹主动脉瘤形成

KE Yi-lang

doi:10.3969/j.issn.1009-8933.2025.03.005

摘要：Background Abdominal aortic aneurysm(AAA)is a life-threatening vascular disease associated with endothe-lial cell senescence.Resveratrol(RSV),a natural polyphenol,exerts potent anti-senescent and anti-inflammatory ef-fects.However,its molecular mechanism in treating AAA remains unclear.Methods An AAA model was estab-lished in mice via angiotensin II(AngII)infusion[1000 ng/(kg·min)],with a subset receiving RSV treatment[100 mg/(kg·day)by gavage].Aortic diameter was measured,and histopathological changes were assessed by Hematox-ylin-Eosin(HE)and Elastica Van Gieson(EVG)staining.Vascular aging was evaluated by senescence-associated β-galactosidase(SA-β-gal)activity and pulse wave velocity(PWV).In vitro,human umbilical vein endothelial cells(HUVECs)were treated with Ang II(10-6 M)with or without RSV(40 μM)and/or the sirtuin 1(SIRT1)inhibi-tor EX527(10 μM).Senescence markers,senescence-associated secretory phenotype(SASP)factor expression[in-terleukin-1 beta(IL-1β),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)],and SIRT1/p21 pathway pro-teins were analyzed.Results In vivo,RSV significantly attenuated Ang II-induced AAA formation,reducing aor-tic diameter,preserving elastic fiber integrity,and suppressing vascular senescence and stiffness.In HUVECs,Ang II-induced senescence and SASP expression were markedly inhibited by RSV.However,these protective effects were abolished by EX527.Mechanistically,RSV reversed the Ang II-induced downregulation of SIRT1 and upregu-lation of p21,which was also blocked by SIRT1 inhibition.Conclusions RSV effectively prevented experimental AAA formation by alleviating vascular aging and endothelial cell senescence.This protective effect was abrogated by the SIRT1 inhibitor EX527,confirming that RSV mitigated AAA development and vascular senescence through the SIRT1/p21 signaling pathway.These findings highlighted RSV as a promising therapeutic candidate for AAA treatment.[S Chin J Cardiol 2025;26(3):173-182]