腹主动脉瘤（AAA）是严重威胁人类健康的老年退行性疾病，国内外发病率均在急剧上升，其病因学至今未明，致使药物开发、生物治疗等非手术干预无有效靶点。动物实验探索干细胞输注治疗AAA取得了肯定的效果；但有关人AAA病变组织的研究却显示，其干细胞数量并未减少，间充质干细胞（MSC）事实上没有发挥其组织再生修复和免疫抑制作用，反而起了促炎性反应的作用。文献回顾中我们发现干细胞治疗AAA的实验动物研究均没有考虑到人AAA是一种老年退行性变这一因素，同时局部炎性环境的影响使得干细胞在不同Toll样受体的作用下呈现出截然相反的两种作用。因此，衰老及所处环境的影响可能是解释人AAA组织中干细胞表现的重要原因之一，也是影响将来干临床应用中干细胞疗效的重要因素之一。本研究通过研究SIRT1/FOXO1与TLR-4/PI3K/Akt通路crosstalk，实现对AAA间充质干细胞功能及其稳态恢复的协同调控。

Abdominal aortic aneurysm(AAA) is a aged degenerative disease with life-threatening complication. The mechanism still remains unclear. This makes the nonoperative intervention like medical or gene therapy very difficult. Emerging studies have used stem cell transplantation to treat AAA, and obtained favorable results. However, as recent study reported, AAA tissue is not short of stem cells, mesenchymal stem cells(MSC) present no immunomoderatory function, rather an inflammatory activity, indicating the stem cells failed to exert their function of repair and anti-autoimmunity, or even take a role to promot AAA dilation. From the literature, we found that previous animal studies did not take AAA as a aged disease and miro-enviroment into account.Since MSCs express Toll-like receptors,upon the activiation by different ligand, they present a polarization into either pro-inflammatory or immuno- suppressive phenotype. This is probably the reason how stem cell act in AAA tissue, and this may also be the factor influencing the result of stem cell therapy after auto-transplantation. The present study is aimed identify the role of SIRT1/FOXO1 and TLR-4/PI3k/Akt crosstalk in regulation of functional disturbance and restoration of MSC.