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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4082102, 14 pages
Research Article

Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction

1Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China

Correspondence should be addressed to Qiaobing Huang; nc.ude.ums@gnib and Zhongqing Chen; moc.361@8002nehcgniqgnohz

Received 22 May 2017; Revised 16 August 2017; Accepted 12 September 2017; Published 25 October 2017

Academic Editor: Andreas Daiber

Copyright © 2017 Weijin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice. The RAGE antibody could also diminish the downregulation and ubiquitination of Sirt1 in LPS-exposed human umbilical vein endothelial cells. An LPS-induced decrease in Sirt1 activity was attenuated by the RAGE antibody and TLR4 inhibitor. In vivo study also demonstrated the attenuating role of Sirt1 and RAGE knockout in LPS-induced increases in dextran leakage of mesenteric venules. Furthermore, activation of Sirt1 prevented LPS-induced decreases in the activity and expression of superoxide dismutase 2, as well as the increases in NADPH oxidase 4 and reactive oxygen species, while inhibition of Sirt1 aggravated the SOD2 decline. It also demonstrated that Sirt1-deacetylated p53 is required for p53 inactivation, which reversed the downregulation of β-catenin caused by LPS.