| Project/Area Number |
18591497
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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 | Akita University |
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Principal Investigator |
UCHINAMI Hiroshi Akita University, School of medicine, Assistant Professor (40400486)
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| Co-Investigator(Kenkyū-buntansha) |
IIDA Masatake Akita University, School of medicine, Assistant Professor (90372325)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,070,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥570,000)
Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Liver Sureer / Stress Response |
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| Research Abstract |
Ischemia-reperfusion (I/R) injury of the liver is one of major problems after extended hepatectomy or liver transplantation. To perform operation much safer, some strategies to prevent I/R injury has been required.
Nrf2 is a transcription factor that protects cell and tissues from oxidative stress by activating protective antioxidant and detoxifying enzymes. It is likely that preoperative activation of Nrf2 in liver-consisting cells results in prevention of I/R injury of the liver. In this protocol, we evaluated whether Nrf2 activation confer the tolerance for I/R injury of the liver.
Oltipraz, 15-deoxy-Δ 12, 14-prostagrandine J2 (PGJ2), and diallyl sulfide (DAS) were used to confirm whether these drugs activate Nrf2 in liver-consisting cells. Liver epithelial cells and liver stellate cells were isolated from rat and mouse liver and cultured. Immunofluorescent assay revealed that Nrf-2 translocated into the nucleus immediately after stimulating by these drugs in both types of cells. The expression of HO-1 was also induced by PGJ2 in a dose dependent manner.
It has been reported that activation of stellate cells has detrimental effect during hepatic I/R. To evaluate the effect of PGJ2 on stellate cell activation, the mRNA expression of alpha smooth muscle actin and type I collagen was examined by real time PCR. PGJ2 significantly inhibited the expression of both genes, suggesting that PGJ2 effectively suppressed the activation of stellate cells.
Finally, the effect of PGJ2 on I/R injury was examined. C57/B16 mouse was used. We applied 70% ischemia model (60 min). PGJ2 was administrated intravenously via tail vein 3 hours before ischemia.
The increasing of AST/ALT level 3 and 6 hours after reperfusion was significantly suppressed by PGJ2. In addition, TUNEL assay revealed that apoptosis after I/R was also suppressed.
These data suggested that Nrf2 activation by PGJ2 may bring the beneficial effect in the field of liver surgery.
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