摘要Abdominal aortic aneurysm(AAA)is a degenerative disease that caused mortality in people aged＞65.Senescence plays a critical role in AAA pathogenesis.Advances in AAA repair techniques have occurred,but a remaining priority is therapies to limit AAA growth and rupture.Our Previous study found cyclic nucleotide phosphodiesterase 1C(PDE1C)exacerbate AAA through aggravate vascular smooth muscle cells(VSMCs)senescence by downregulating Sirtuin1(SIRT1)expression and activity.Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation,it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA.This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice.In addition,the elastin degradation,MMP(matrix metalloproteinase)activity,macrophage infiltration,ROS production,collagen fibers remodeling,and VSMCs senescence were decreased in AAA treated with vinpocetine.While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice.Accordingly,we revealed that vinpocetine suppressed migration,proliferation,and senescence in VSMCs.Moreover,vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy.In conclusion,this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.