Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis
Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis
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DOI：
10.1152/ajpgi.1997.273.1.g124
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发表时间：
1997-07-01
影响因子：
4.5
通讯作者：
Chung, JJ
中科院分区：
文献类型：
--
作者：
Rockey, DC;Chung, JJ
在细胞因子和/或脂多糖的刺激下，肝脏中通过诱导型一氧化氮合酶(INOS)产生的一氧化氮(NO)显著增加。本研究的目的是探讨在毒素介导和梗阻性肝损伤和纤维化形成过程中，特定肝细胞群通过诱导型一氧化氮合酶产生一氧化氮的情况。单次给予四氯化碳后，仅在枯否细胞中检测到iNOS mRNA和亚硝酸盐(NO的代谢产物)。在反复给予四氯化碳后，在任何细胞类型中都检测不到它们，包括患有晚期肝硬变(即门脉高压和/或腹水)的动物。胆管结扎是一种不同的肝损伤和纤维化机制，在所有非实质细胞中均可检测到iNOS mRNA和亚硝酸盐，但在肝细胞中未检测到iNOS mRNA和亚硝酸盐。胆管结扎后24小时，枯否细胞iNOS m RNA和NO生成量最大，但长时间结扎胆管后，iNOS主要分布在肝窦内皮细胞。这些数据表明，iNOS在损伤后肝脏中的表达在时间和空间上都有所不同，并且随着伤害类型的不同而不同。
Nitric oxide (NO) production via inducible NO synthase (iNOS) is prominent in the liver after stimulation with cytokines and/or lipopolysaccharide. The aim of this study was to investigate the production of NO via iNOS in specific liver cell populations during toxin-mediated and obstructive hepatic injury and fibrogenesis. After a single dose of carbon tetrachloride, iNOS mRNA and nitrite (a metabolic product of NO) were detected only in Kupffer cells. They were not detectable in any cell type after recurrent administration of carbon tetrachloride, including in animals with far advanced cirrhosis (i.e., portal hypertension and/or ascites). After bile duct ligation, a mechanistically different form of liver injury and fibrogenesis, iNOS mRNA and nitrite were identified in all nonparenchymal cells but not in hepatocytes. Twenty-four hours after bile duct Ligation, iNOS mRNA and NO production were greatest in Kupffer cells, but after prolonged bile duct ligation, iNOS was found predominantly in sinusoidal endothelial cells. These data indicate that iNOS expression varies temporally and spatially in the liver after injury and also varies with the type of insult.