Wojewodzka-Zelezniakowicz Marzena, Gromotowicz-Poplawska Anna, Kisiel Wioleta, Konarzewska Emilia, Szemraj Janusz, Ladny Jerzy Robert, Chabielska Ewa
1 Department of Emergency and Disaster Medicine, Medical University of Bialystok, Poland.
2 Department of Biopharmacy, Medical University of Bialystok, Poland.
J Renin Angiotensin Aldosterone Syst. 2017 Jan;18(1):1470320316687197. doi: 10.1177/1470320316687197.
The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro.
We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10 M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (HO and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO/NO concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs).
We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is.
This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.
本研究旨在探讨血浆和组织血管紧张素转换酶抑制剂（ACE-Is）对丙泊酚诱导的内皮功能障碍的影响，并在体外阐明其相关机制。
我们检测了丙泊酚（50 μM）、喹那普利拉和依那普利拉（10 μM）对人脐静脉内皮细胞（HUVECs）纤溶功能（组织型纤溶酶原激活物、纤溶酶原激活物抑制剂-1、凝血酶激活的纤溶抑制物抗原水平）、氧化应激参数（过氧化氢和丙二醛抗原水平以及超氧化物歧化酶和烟酰胺腺嘌呤二核苷酸磷酸氧化酶mRNA水平）和一氧化氮生物利用度（NO/NO浓度以及mRNA水平的一氧化氮合酶表达）的影响。
我们发现两种ACE-Is在体外均促进了相似的内皮纤溶特性并降低了氧化应激。单独使用丙泊酚会增加内皮细胞抗纤溶和促氧化因子的释放，并增加诱导型一氧化氮合酶mRNA的表达。我们还发现，在ACE-Is预孵育后用丙泊酚孵育HUVECs会导致丙泊酚的抗纤溶和促氧化潜能减弱，且两种ACE-Is作用后的效果相似。
该观察结果表明，所研究的ACE-Is对丙泊酚引起的内皮细胞功能障碍具有保护作用，且与血流动力学无关。
