Takahashi H, Johansson I, French S W, Ingelman-Sundberg M
Department of Pathology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
Pharmacol Toxicol. 1992 May;70(5 Pt 1):347-51. doi: 10.1111/j.1600-0773.1992.tb00485.x.
We studied the effects of dietary fat composition on the activities of the microsomal ethanol oxidizing system (MEOS), paranitrophenol hydroxylase (PH) activity and ethanol-inducible cytochrome P450 isozymes (CYP2E1 and CYP2B1) in the liver of rats to determine the role of this ethanol metabolizing pathway in the pathogenesis of alcoholic liver disease (ALD). Wistar male rats were pair-fed a liquid diet, containing either tallow (TF) or corn oil (CF) as the fat component, and ethanol or an isocaloric amount of dextrose, through an implanted intragastric cannula. Liver pathology of rats fed ethanol (CF-ALC) and CF diet showed severe fatty change whereas the rats fed TF-alcohol and the TF and CF controls did not. MEOS activity of the CF-ALC group was 8 times of that in the CF-CTL group (P less than 0.01). In TF-ALC rats, MEOS activity was increased to 2.6 times compared to that of TF-CTL (P less than 0.01). ApoCYP2E1 in CF-ALC and TF-ALC were 818 +/- 63 and 433 +/- 1- pmol/mg protein, respectively, and these values were significantly higher when compared with those of the pair-fed controls (P less than 0.005). In contrast, apoCYP2B1 was increased to an equal degree in both CF-ALC and TF-ALC. When PH-activity was measured, the level of activity on TF-ALC rats did not differ from that of CF-ALC rats. Thus, ethanol-induction of apoCYP2B1 (2x) and PH (6-8x) were the same for CF and TF (2x); but not for apoCYP2E1 (21 and 8x, respectively) and MEOS activity (8 and 2.6x, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了饮食脂肪成分对大鼠肝脏微粒体乙醇氧化系统（MEOS）活性、对硝基苯酚羟化酶（PH）活性以及乙醇诱导的细胞色素P450同工酶（CYP2E1和CYP2B1）的影响，以确定这条乙醇代谢途径在酒精性肝病（ALD）发病机制中的作用。通过植入的胃内插管，将Wistar雄性大鼠成对喂食含牛脂（TF）或玉米油（CF）作为脂肪成分的液体饮食，并分别添加乙醇或等热量的葡萄糖。喂食乙醇（CF-ALC）和CF饮食的大鼠肝脏病理显示严重脂肪变性，而喂食TF-酒精以及TF和CF对照组的大鼠则未出现。CF-ALC组的MEOS活性是CF-CTL组的8倍（P<0.01）。在TF-ALC大鼠中，MEOS活性相较于TF-CTL增加到2.6倍（P<0.01）。CF-ALC和TF-ALC中的载脂蛋白CYP2E1分别为818±63和433±1 pmol/mg蛋白，与成对喂食的对照组相比，这些值显著更高（P<0.005）。相比之下，CF-ALC和TF-ALC中的载脂蛋白CYP2B1增加程度相同。测量PH活性时，TF-ALC大鼠的活性水平与CF-ALC大鼠无异。因此，CF和TF对载脂蛋白CYP2B1（2倍）和PH（6 - 8倍）乙醇诱导作用相同；但对载脂蛋白CYP2E1（分别为21倍和8倍）和MEOS活性（分别为8倍和2.6倍）诱导作用不同。（摘要截断于250字）
