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白藜芦醇可抑制人炎症性脂肪组织体外模型中 PAI-1 基因的表达。

Resveratrol suppresses PAI-1 gene expression in a human in vitro model of inflamed adipose tissue.

机构信息

Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

出版信息

Oxid Med Cell Longev. 2013;2013:793525. doi: 10.1155/2013/793525. Epub 2013 Jun 2.

Abstract

Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF κ B pathway. Together, resveratrol can act as NF κ B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.

摘要

纤溶酶原激活物抑制剂-1(PAI-1)水平升高与许多病理生理并发症有关;其中包括肥胖症。白藜芦醇被提议改善与肥胖相关的健康问题,但白藜芦醇对肥胖症中 PAI-1 基因表达的影响尚不完全清楚。在这项研究中,我们使用 SGBS 脂肪细胞和人脂肪组织炎症模型来研究白藜芦醇对 PAI-1 产生的影响。白藜芦醇处理 SGBS 脂肪细胞可使 PAI-1 mRNA 和蛋白的表达呈时间和浓度依赖性降低。进一步的实验表明,与肥胖相关的炎症条件会导致 PAI-1 基因表达上调,而白藜芦醇则拮抗了这种上调。尽管在非炎症条件下,PI3K、Sirt1、AMPK、ROS 和 Nrf2 信号通路似乎在调节 PAI-1 基因表达中发挥了重要作用,但这些信号通路成分并未参与介导白藜芦醇对 PAI-1 产生的影响在炎症条件下。相反,我们证明,白藜芦醇在炎症条件下对 PAI-1 诱导的作用是通过抑制 NF κ B 通路介导的。总之,白藜芦醇可以作为脂肪细胞中的 NF κ B 抑制剂,因此炎症脂肪组织中 PAI-1 表达的降低可能为肥胖症的新治疗选择提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213c/3684090/2cf3d8e31838/OXIMED2013-793525.001.jpg

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