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2017 Fiscal Year Final Research Report

Identification of novel treatment and biomarkers based on pharmacokinetics in patients with hepatocellular carcinoma

Research Project

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Project/Area Number 15K08077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionNara Medical University

Principal Investigator

Namisaki Tadashi  奈良県立医科大学, 医学部, 講師 (20526850)

Co-Investigator(Kenkyū-buntansha) 野口 隆一  奈良県立医科大学, 医学部附属病院, 研究員 (30423908)
吉治 仁志  奈良県立医科大学, 医学部, 教授 (40336855)
北出 光輝  奈良県立医科大学, 医学部, 学内講師 (40526795)
Co-Investigator(Renkei-kenkyūsha) Moriya Kei  奈良県立医科大学, 医学部, 講師 (40526852)
Research Collaborator Nishimura Norihisa  奈良県立医科大学, 医学部附属病院, 研究員
Project Period (FY) 2015-04-01 – 2018-03-31
Keywords胆汁酸
Outline of Final Research Achievements

We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker (ARB) on hepatic fibrogenesis in rat model of NASH.The in vitro and in vivo effects of an FXR agonist (INT747 at 30 mg/kg/day) and an ARB (Losartan: 30 mg/kg/day) on hepatic fibrogenesis were evaluated.In PS-administered OLETF rats, INT747 and losartan had potent inhibitory effects on hepatic fibrogenesis with suppression of HSC activation and expression of transforming growth factor (TGF)-β1 and TLR4. INT747 decreased intestinal permeability by ameliorating zonula occuludens-1 (ZO-1) disruption, whereas losartan directly suppressed the regulation of Ac-HSC. The in vitro and in vivo inhibitory effects of INT747 and losartan on TGF-β1 and TLR4 mRNA expression in Ac-HSC were almost in parallel. Losartan directly inhibited the regulation of Ac-HSC. Combined treatment may represent a promising novel approach for NASH.

Free Research Field

肝臓学

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Published: 2019-03-29  

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