| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Shuji Faculty of Medicine, KYUSHU UNIVERSITY, Associate Professor, 医学部・附属病院, 助教授 (70274454)
YAMAGUCHI Koji Faculty of Medicine, KYUSHU UNIVERSITY, Lecturer, 医学部・附属病院, 講師 (50191226)
CHIJIIWA Kazuo Graduate School of Medical Sciences, KYUSHU UNIVERSITY, Associate Professor, 大学院・医学研究院, 助教授 (90179945)
NAKANO Kenji Faculty of Medicine, KYUSHU UNIVERSITY, Assistant Professor, 医学部・附属病院, 助手 (00315061)
NOSHIRO Hirokazu Faculty of Medicine, KYUSHU UNIVERSITY, Assistant Professor, 医学部・附属病院, 助手 (90301340)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
The activities of hepatic cholesterol 7α-hydroxylase have been considered to be regulated by the amount and composition of bile acids returning to the liver via the portal vein. However, recent findings suggested that passage of bile salts through the gastrointestinal tract is necessary for its regulation. The aim of this study was to examine the location of the putative intestinal factor (luminar factor, mucosal factor, or bile acid metabolites) that regulates the cholesterol 7α-hydroxylase activity in rats. A polyethylene tube was inserted into the common bile duct and another side of the tube was placed in the duodenum (DD), lower jejunum (JD), cecum (CeD), or transverse colon (CoD) as internal biliary bypass models and in the urinary bladder as external biliary drainage (ED). After bile diversion for 7 days, rats were sacrificed and hepatic cholesterol 7α-hydroxylase activities were determined. Biliary, serum, and portal bile acid concentrations, biliary bile acid composition, and
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intestinal absorption of labeled taurocholic acid were analyzed. Hepatic cholesterol 7α-hydroxylase activity was not changed in the DD and JD groups, however, it was significantly up-regulated in the CeD (227 % of the controls), CoD (312 %), and ED groups (316 %). Biliary, serum, and portal bile acid concentrations were not significantly changed in the DD, JD, and CeD groups but those were significantly lower in the CoD and ED groups. The proportion of the secondary bile acids was significantly increased in the CeD group and was decreased in the CoD and ED groups. Intestinal absorption of labeled taurocholic acid was almost 100 % in the JD group, 56 % in the CeD group, and 23 % in the CoD group. As the cholesterol 7α-hydroxylase activity was not significantly changed in the JD group and the predominance of secondary bile acids did not suppress the enzyme activity in the CeD group, it was concluded that the luminar factor and the bile acid metabolites may not be the intestinal factor. The cholesterol 7α-hydroxylase activity is likely to be regulated by the mucosal factor, which is linked to the intestinal bile acid absorption, but not by the bile acids themselves, because the portal bile acid concentration did not correlate with the enzyme activity. Less
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