Kuo P C, Abe K Y
Department of Surgery, Stanford University Medical Center, California, USA.
Gastroenterology. 1995 Jul;109(1):206-16. doi: 10.1016/0016-5085(95)90286-4.
BACKGROUND & AIMS: Nitric oxide modifies free radical-mediated cell processes in multiple in vivo and in vitro systems. The aim of this study was to determine the role of hepatocyte production of NO in oxidative injury.
Rat hepatocytes in primary culture were incubated with 1,2,3-benzenetriol, a source of superoxide. Interleukin (IL) 1 was added to induce NO synthesis. Injury was determined by aspartate aminotransferase (AST), malondialdehyde (MDA), and glutathione (GSH) levels.
Benzenetriol-induced injury increased AST and MDA levels and decreased GSH levels in control and IL-1-treated cells. Inhibition of NO synthesis in IL-1-treated cells significantly increased AST and MDA production while enhancing GSH depletion. In the presence of superoxide dismutase or S-nitroso-albumin, an exogenous source of NO, injury was decreased or abolished. NO production was significantly increased with oxidative stress. In benzenetriol-induced injury in IL-1-stimulated hepatocytes, reverse-transcription polymerase chain reaction showed significantly increased levels of inducible NO synthase messenger RNA, whereas immunoblot analysis showed similarly increased levels of inducible NO synthase protein.
In this rat hepatocyte model of IL-1/benzenetriol-mediated injury, NO, derived from endogenous synthesis or an exogenous donor, is protective. Oxidative stress may have a role in the transcriptional control of NO synthesis.
一氧化氮在多种体内和体外系统中可调节自由基介导的细胞过程。本研究旨在确定肝细胞产生一氧化氮在氧化损伤中的作用。
将原代培养的大鼠肝细胞与超氧化物来源的1,2,3 -苯三酚一起孵育。添加白细胞介素（IL）-1以诱导一氧化氮合成。通过天冬氨酸转氨酶（AST）、丙二醛（MDA）和谷胱甘肽（GSH）水平来确定损伤情况。
苯三酚诱导的损伤使对照细胞和IL - 1处理的细胞中AST和MDA水平升高，GSH水平降低。在IL - 1处理的细胞中抑制一氧化氮合成可显著增加AST和MDA的产生，同时增强GSH的消耗。在超氧化物歧化酶或S -亚硝基白蛋白（一种外源性一氧化氮来源）存在的情况下，损伤减少或消除。氧化应激时一氧化氮生成显著增加。在IL - 1刺激的肝细胞中苯三酚诱导的损伤中，逆转录聚合酶链反应显示诱导型一氧化氮合酶信使核糖核酸水平显著升高，而免疫印迹分析显示诱导型一氧化氮合酶蛋白水平同样升高。
在这个IL - 1/苯三酚介导损伤的大鼠肝细胞模型中，内源性合成或外源性供体产生的一氧化氮具有保护作用。氧化应激可能在一氧化氮合成的转录调控中起作用。
