Nanji A A, Griniuviene B, Yacoub L K, Fogt F, Tahan S R
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts, USA.
Exp Mol Pathol. 1995 Feb;62(1):42-51. doi: 10.1006/exmp.1995.1005.
We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship among intercellular adhesion molecule-1 (ICAM-1) expression, tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin, and inflammatory changes in the liver. Rats were fed different dietary fats (saturated fat, corn oil, and fish oil) with ethanol; control rats were fed isocaloric amounts of dextrose instead of ethanol. At sacrifice the following were evaluated: liver pathologic changes, TNF-alpha mRNA by reverse transcription-PCR, plasma endotoxin, and ICAM-1 by immunohistochemistry and immunoblot analysis. Upregulation of ICAM-1 in endothelial lining cells in central and portal veins was observed in rats showing evidence of pathologic changes. Rats fed fish oil and ethanol, which exhibited the most severe inflammation, also showed hepatocyte ICAM-1 staining. The presence of ICAM-1 staining, in general, correlated with the level of TNF-alpha mRNA expression and plasma endotoxin levels. Upregulation of ICAM-1 in rats fed ethanol may contribute to the inflammatory changes seen in this model. The association between ICAM-1 upregulation and endotoxin and TNF-alpha mRNA suggests a role for these mediators in the inflammatory process in alcoholic liver injury.
我们使用酒精性肝病的大鼠灌胃模型来评估细胞间黏附分子-1(ICAM-1)表达、肿瘤坏死因子-α(TNF-α)、血浆内毒素与肝脏炎症变化之间的关系。给大鼠喂食含乙醇的不同膳食脂肪(饱和脂肪、玉米油和鱼油);对照大鼠喂食等热量的葡萄糖而非乙醇。处死大鼠时,评估以下指标:肝脏病理变化、通过逆转录-聚合酶链反应检测TNF-α mRNA、血浆内毒素,以及通过免疫组织化学和免疫印迹分析检测ICAM-1。在显示有病理变化迹象的大鼠中,观察到中央静脉和门静脉内皮衬里细胞中ICAM-1上调。喂食鱼油和乙醇的大鼠炎症最为严重,其肝细胞也显示有ICAM-1染色。一般来说,ICAM-1染色的存在与TNF-α mRNA表达水平和血浆内毒素水平相关。喂食乙醇的大鼠中ICAM-1上调可能导致该模型中出现的炎症变化。ICAM-1上调与内毒素和TNF-α mRNA之间的关联表明这些介质在酒精性肝损伤的炎症过程中起作用。