Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production

Ming Chung Lin, Chiou-Feng Lin, Chien Feng Li, Ding Ping Sun, Li Yun Wang, Chung-Hsi Hsing

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

原文英語
頁(從 - 到)12092-12107
頁數16
期刊International Journal of Molecular Sciences
16
發行號6
DOIs
出版狀態已發佈 - 五月 27 2015

ASJC Scopus subject areas

  • 物理與理論化學
  • 有機化學
  • 光譜
  • 無機化學
  • 催化
  • 分子生物學
  • 電腦科學應用

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