| Project/Area Number |
23590987
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nara Medical University |
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Principal Investigator |
FUKUI HIROSHI 奈良県立医科大学, 医学部, 教授 (80145838)
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| Co-Investigator(Renkei-kenkyūsha) |
YOSHIJI Hitoshi 奈良県立医科大学, 医学科, 准教授 (40336855)
FUJIMOTO Masao 奈良県立医科大学, 医学科, 講師 (60295805)
NAMISAKI Tadashi 奈良県立医科大学, 医学科, 助教 (20526850)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | エンドトキシン / 自然免疫 / Toll-like受容体 / 非アルコール性脂肪肝炎 / 腸管相関 / 難吸収性抗菌薬 / ウルソデオキシコール酸 / 急性肝不全 / TNF-α |
|---|
| Research Abstract |
The underling cause of nonalcoholic steatohepatitis is still unlear, but intestinal bacterial flora and endotoxin are important factors. We evaluated pathogenic roles of endotoxin, intestinal permeability and innate immunity on the development of liver fibrosis in rats fed choline-deficient and amino acid-defined (CDAA) diet. In these rats, marked fibrosis was associated with increased intestinal permeability, augmented development of Toll-like recrptor 4 (TLR4) mRNA, lipopolysaccharide binding protein (LBP) mRNA and TNF-alpha mRNA in the liver. Oral administrations of nonabsorbable antibiotics for selective bowel decontamination and ursodeoxycholic acids were demonstrated to suppress intestinal permeability and TLR4 mediated inflammation and finally inhibit progression of fibrosis. Regulation of gut-liver axis may become a new strategy for prevention of human steatohepatitis.
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