論文

基本情報

氏名 安武 健一郎
氏名(カナ) ヤスタケ ケンイチロウ
氏名(英語) YASUTAKE KENICHIRO
所属 中村学園大学 栄養科学部 栄養科学科
職名 准教授

題名

Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARa–MDR3 pathway

単著・共著の別

 

著者

Nakamuta M
Fujino T
Yada R
Yasutake K
Yoshimoto T
Harada N
Yada M
Higuchi N
Kato M
Kohjima M
Taketomi A
Maehara Y
Nakashima M
Kotoh K
Enjoji M

担当区分

 

概要

Objective: Bezafibrate (BF) has been used to treat biliary damage, particularly in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has been demonstrated. The mechanism of action is thought to involve activation of the PPAR alpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this hypothesis in patients with hepatobiliary disease. Methods: The levels of serum gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile components were examined before and after BF administration in patients with obstructive jaundice undergoing percutaneous transhepatic biliary drainage (PTBD). Hepatic expression of PPAR alpha and MDR3 was quantified by real-time PCR in patients with PBC or non-alcoholic fatty liver disease (NAFLD). Results: In patients with obstructive jaundice, BF decreased the scrum levels of biliary enzymes and increased the bile concentration of PL. In patients with PBC or NAFLD, the expression levels of MDR3 were already up-regulated before starting the BF treatment. Although BF treatment did not further up-regulate MDR3 expression in NAFLD patients, PPAR alpha expression was significantly increased. Conclusions: BF enhanced the secretion of PL into bile in cholestatic patients undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent cholesterol overload, MDR3 was already expressed at a high level to compensate for bile acids overproduction, and its expression was hardly affected by BF. In patients with chronic liver diseases such as PBC, BF may induce clinical effects via mechanisms independent of PL secretion.

発表雑誌等の名称

Int J Clin Pharmacol Therapeut

出版者

DUSTRI-VERLAG DR KARL FEISTLE

48

1

開始ページ

22

終了ページ

28

発行又は発表の年月

2010-01

査読の有無

無し

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

 

国際共著

 

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無償ダウンロード

無償ダウンロード不可

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