Makino I, Chijiiwa K, Fukushima K, Kameoka N, Komura M, Kuroki S, Yamashita H, Tanaka M
Department of Surgery 1, Kyushu University Faculty of Medicine, Fukuoka, Japan.
J Surg Res. 1997 Mar;68(2):91-8. doi: 10.1006/jsre.1997.5048.
To examine the regulatory effect of bile acid level on bile acid synthesis in the liver.
The portal branch perfusing left lateral and median lobes of the liver was ligated in rats and the activities of hepatic microsomal cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile acid synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and intrahepatic concentrations of cholesterol and bile acids were determined in the liver lobes deprived of and supplied with portal blood on Days 0, 1, 2, 4, and 7 after selective portal vein ligation (SPVL).
In the portal vein (PV)-ligated lobes, liver weight decreased, hepatic cholesterol concentration was unchanged, and microsomal cholesterol concentration increased after SPVL. In the PV-nonligated lobes, liver weight increased, hepatic cholesterol concentration increased, and microsomal cholesterol concentration was unchanged. There were no significant differences in the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase among the PV-ligated and PV-nonligated lobes and the sham-operated controls. Intrahepatic bile acid level increased significantly in the PV-nonligated lobes for 4 days after SPVL, whereas those were essentially constant in the PV-ligated and the sham-operated control liver. Despite significant changes in the concentrations of intrahepatic cholesterol and bile acid, no significant correlations were observed between these concentrations and the activities of cholesterol 7 alpha-hydroxylase.
SPVL causes atrophy and hypertrophy of the PV-ligated and nonligated liver lobes, respectively, without any significant changes in cholesterol and bile acid synthesis. Intrahepatic concentrations of bile acids and cholesterol have no regulatory effect on cholesterol 7 alpha-hydroxylase activity in the SPVL rat model.
研究胆汁酸水平对肝脏胆汁酸合成的调节作用。
结扎大鼠肝脏左外叶和中叶的门静脉分支,在选择性门静脉结扎(SPVL)后第0、1、2、4和7天,测定缺血和供血肝叶中胆汁酸合成限速酶肝微粒体胆固醇7α-羟化酶、3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶的活性,以及肝内胆固醇和胆汁酸的浓度。
在门静脉结扎的肝叶中,SPVL后肝脏重量减轻,肝胆固醇浓度不变,微粒体胆固醇浓度升高。在未结扎门静脉的肝叶中,肝脏重量增加,肝胆固醇浓度升高,微粒体胆固醇浓度不变。门静脉结扎和未结扎的肝叶以及假手术对照组之间,HMG-CoA还原酶和胆固醇7α-羟化酶的活性没有显著差异。SPVL后4天,未结扎门静脉的肝叶肝内胆汁酸水平显著升高,而在门静脉结扎的肝叶和假手术对照肝脏中,胆汁酸水平基本保持恒定。尽管肝内胆固醇和胆汁酸浓度发生了显著变化,但这些浓度与胆固醇7α-羟化酶的活性之间未观察到显著相关性。
SPVL分别导致门静脉结扎和未结扎的肝叶萎缩和肥大,而胆固醇和胆汁酸合成无显著变化。在SPVL大鼠模型中,肝内胆汁酸和胆固醇浓度对胆固醇7α-羟化酶活性无调节作用。