| Project/Area Number |
14571208
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
KUROKI Syoji Kyushu University Hospital, Lecturer, 大学病院, 講師 (30215090)
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| Co-Investigator(Kenkyū-buntansha) |
NOSHIRO Hirokazu Kyushu University Hospital, Associate Professor, 大学病院, 助手 (90301340)
SHIMIZU Shuji Kyushu University Hospital, Associate Professor, 大学病院, 助教授 (70274454)
CHIJIWA Kazuo Miyazaki University, Faculty of Medicine, Professor, 医学部, 教授 (90179945)
OHSHIMA Akira Kyushu University Hospital, Associate Professor, 大学病院, 助手 (70335959)
NAKANO Kenji Kyushu University Hospital, Associate Professor, 大学病院, 助手 (00315061)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | bile acid synthesis / regulation mechanism / cholesterol 7α-hydroxylase / bile acid metabolism / intestinal factor / rat / コレステロール7α酸化酵素 |
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| Research Abstract |
Cholesterol 7α-hydroxylase (CYP7A1) is regulated by bile acids through farnesoid X receptor (FXR) mechanism in the negative feedback fashion. However, the fact that CYP7A1 is down-regulated by intraduodenal administration of bile acid but not by intravenous administration may not be explained only by this mechanism. The aim of this study was to establish a new rat model with reconstructed or simulated enterohepatic circulation to examine if intravenous or portal administration of bile acid can regulate CYP7A1. Under biliary drainage, taurocholate (0 or 6 μ mol/hour/100 g body weight) was administered continuously for 48 hours into the duodenum (ID-0/ID-6), femoral vein (IV-0/IV-6), or portal vein (IP-0/IP-6) to make a condition in which biliary bile acids are continuously lost and similar dose of taurocholate is supplied to the liver simultaneous CYP7A1 activity and mRNA expression, of the ID-0 group were significantly increased compared with the no treatment (NT) group. CYP7A1 activity and mRNA expression of the ID-6 group were suppressed significantly to 41% and 46% of those of the ID-0 group, respectively. In the IV-6 and IP-6 groups, however, the enzyme activity and mRNA expression were decreased slightly, but the suppression was not statistically significant. The results suggested that portal as well as intravenous administration of bile acids cannot suppress the bile acid synthesis as effectively as intraduodenal administration. It was concluded that an unidentified regulatory factor other than the nuclear receptors may be involved in the bile acids synthesis in vivo.
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