| Project/Area Number |
23390161
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Chubu University (2012-2013)
Nagoya University (2011) |
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Principal Investigator |
NASU Tamie 中部大学, 生命健康科学部, 教授 (10020794)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Akira 名古屋大学, 医学系研究科, 教授 (30252175)
NAITO Hisao 名古屋大学, 医学系研究科, 助教 (90547556)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | SHRSP5/Dmcrラット / 高脂肪・高コレステロール食 / 肝炎 / 線維化 / エイコサペンタエン酸 / ウルソデオキシコール酸 / バイオマーカー / 胆汁酸 / SHRSP5/Dmcr / コレステロール / コール酸 / ケノデオキシコール酸 / デオキシコール酸 / リトコール酸 / 線維症進展 / 肝線維症 / M30抗原 / 壊死 / カスパーゼ3/7 / 高脂肪食 / SHRSP / Wistar Kyoto / 脂肪感 / 炎症 / 性差 |
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| Research Abstract |
High-fat and-cholesterol diet (HFC) induced hepatic fibrosis greater in SHRSP5/Dmcr than SHRSP. This was due to greater suppression of UGT, CAR and PXR in the former than the latter. The fibrosis area was greater in males than females. The UGT activity and expressions of CAR and PXR, were not suppressed by HFC diet in females, while significantly suppressed in males, suggesting this enzyme and its nuclea receptors excreting bile acid may be one of important role in the sex differences in the histopathological finding. EPA prevented inflammation by inhibiting increase of p65/p50, however, did not influence fibrosis development.
HFC diet mainly induced necrosis in the liver by decrease in caspase 3/7 activity. Serum K18Asp396 levels were positively correlated with hepatocyte necrosis and fibrosis, suggesting that the levels may be a good noninvasive biomarker of these findingss. According to HFC-diet feeding, ratio of cholic acid/chenodeoxycholic acid (CDCA)significantly decreased.
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