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腹主动脉瘤(AAA):抗氧化剂在预防和治疗中的作用如何?

Abdominal Aortic Aneurysm (AAA): Is There a Role for the Prevention and Therapy Using Antioxidants?

机构信息

Department of Cardiovascular Surgery, Surgical Research Center (CREDEC) and Plateforme Nutrition Antioxydante et Santé, University Hospital of Liege, Sart Tilman, 4000 Liege, Belgium.

出版信息

Curr Drug Targets. 2018;19(11):1256-1264. doi: 10.2174/1389450118666170918164601.

Abstract

BACKGROUND

Abdominal aortic aneurysm (AAA) is a degenerative disease that causes mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seem to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin.

OBJECTIVES

Human studies confirmed that oxidative stress and endothelial dysfunction, an important source of ROS production, were well associated with AAA development. Reducing oxidative stress by antioxidants can therefore be a good strategy for limiting AAA development. The objective of the present study is to review literature data favoring or not such a hypothesis. There is currently no evidence showing that strategies using classical low molecular weight antioxidants (vitamins C and E, β- carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function and also their capacity to stimulate enzymatic antioxidants through activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression.

CONCLUSION

Clinical studies are therefore urgently necessary to confirm the potential beneficial effect of polyphenols in preventing or limiting AAA.

摘要

背景

腹主动脉瘤(AAA)是一种退行性疾病,会导致 > 65 岁人群死亡。活性氧(ROS)和氧化应激的增加似乎在 AAA 的发病机制中起关键作用。在使用实验模型的主动脉组织中已经确定了几种 ROS 来源:炎症、NAD(P)H 或 NOX 活性增加、诱导型一氧化氮合酶(iNOS)过表达、内皮型一氧化氮合酶(eNOS)解偶联、血小板激活和血红蛋白中铁释放。

目的

人体研究证实,氧化应激和内皮功能障碍(ROS 产生的重要来源)与 AAA 的发展密切相关。因此,通过抗氧化剂来减少氧化应激可能是限制 AAA 发展的一种好策略。本研究旨在综述支持或不支持这种假说的文献数据。目前没有证据表明使用经典的小分子抗氧化剂(维生素 C 和 E、β-胡萝卜素)作为 ROS 靶点的策略可有效降低人类 AAA 的进展。然而,最近的流行病学数据强调了富含抗氧化多酚的饮食在水果中的积极作用。多酚通过恢复内皮功能的能力,以及通过激活 Keap1/Nrf2/ARE 通路刺激酶抗氧化剂的能力,可能成为降低人类 AAA 进展的有前途的治疗靶点。

结论

因此,迫切需要临床研究来证实多酚在预防或限制 AAA 方面的潜在有益作用。

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