Komatsu Y, Shiratori Y, Hikiba Y, Hashimoto N, Han K, Kawase T, Yoshida H, Okano K, Omata M
Department of Internal Medicine II and I, Faculty of Medicine, University of Tokyo, Japan.
Dig Dis Sci. 1996 May;41(5):1030-7. doi: 10.1007/BF02091548.
In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antagonist) on hepatic injury in vivo as well as on neutrophil adherence to hepatic endothelial cells in vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury. Although an enhanced serum TNF-alpha level after GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-alpha, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.
为了阐明血小板活化因子（PAF）在半乳糖胺（GalN）加脂多糖（LPS）诱导的肝损伤发病机制中的作用，我们研究了WEB 2086（PAF受体拮抗剂）对体内肝损伤以及体外中性粒细胞与肝内皮细胞黏附的影响，因为我们最近已经阐明了中性粒细胞在这种肝损伤实验模型中的作用。尽管WEB 2086未能降低GalN-LPS给药后血清TNF-α水平的升高，但WEB 2086减轻了GalN-LPS给药后肝脏中的肝损伤和肝中性粒细胞积聚。一项体外研究表明，在WEB 2086存在的情况下，用GalN-LPS处理的大鼠血清刺激后增强的中性粒细胞与肝内皮细胞的黏附以剂量依赖性方式降低。此外，发现LPS、TNF-α和PAF可增强中性粒细胞与肝内皮细胞的黏附，而在WEB 2086存在的情况下这种黏附会降低。这些结果表明，PAF在GalN-LPS诱导的肝损伤中起重要作用，并且PAF受体拮抗剂可降低中性粒细胞与肝脏中肝内皮细胞的黏附。
