| Project/Area Number |
17591408
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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 | The University of Tokushima |
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Principal Investigator |
FUJII Masahiko The University of Tokushima, Institute of Health Biosciences, Part-time lecturer, 大学院ヘルスバイオサイエンス研究部, 非常勤講師 (20380040)
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| Co-Investigator(Kenkyū-buntansha) |
IMURA Satoru The University of Tokushima, Tokushima University Hospital, Assistant professor, 大学院ヘルスバイオサイエンス研究部, 助手 (90380021)
MORINE Yuji The University of Tokushima, Tokushima University Hospital, Assistant professor, 医学部・歯学部附属病院, 助手 (60398021)
SHIMADA Mitsuo The University of Tokushima, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (10216070)
SUGINO Hiromu The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Massive hepatectomy / liver transplantation / liver regeneration / follistatin / FK506 / in-chin-co-to / fluvastatin / DNA microarray |
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| Research Abstract |
Background)
Liver failure after massive hepatectomy is one of the most important postoperative complication. Furthermore, in outbreak of liver failure after liver tranplantation, small-for-size graft is an important factor. In this study, we conducted to clarify the regulatory mechanism after massive hepatecomy and the control method for postoperative liver failure.
Method and Results)
1. Regulation of ischemic reperfusion injury (I/R injury) of the liver
(1) follistatin
In rat model, improvement of transaminase levels and survival rate were not observed.
(2)fluvastatin
Preoperative treatment (oral administration) of fluvastatin decreased transaminase levels after I/R injury. Furthermore, we confirmed expression of eNOS, several cytokines and NOX4 on realtime PCR method after I/R injury.
2. Gene expression after massive hepatectomy (90%)
We analyzed gene expression after massive hepatectomy using the DNA microarray, and confirmed that Gene expression of STAT3 and HO-1 was enhanced after operati
… More
on.
3. Effect of modulation on liver regeneration after massive hepatectomy
(1)FK506
In massive hepaatectomy (90%) model, FK506 accelerated liver regeneration in 72hr after operation. Furthermore, serum level of FK506 in massive hepatectomy (90%) model was higher than that in 70% hepatectomy model.
(2)In-Chin-co-to (Japanese herbal medicine)
Preoperative treatment (oral administration) of In-Chin-co-to which have effect of acceleration for biliary excretion improved postoperative survival and decreased transaminase levels. Furthermore, In-Chin-co-to accelerated liver regeneration after massive hepatectomy. In immunohisitochemical staining, expression of PCNA and HO-1 was significantly higher and a SMA was significantly lower.
(3) fluvastatin
Preoperative treatment (oral administration) of fluvastatin which have protection effect for I/R injury such as vascular statin accelerated liver regeneration and decreased total-billilubin level afar massive hepatectomy. In immunohisitochemical staining, expression of a SMA was suppressed
Summary)
In this study, we clarified the regulatory mechanism of liver regeneration and effect of several modulators for liver regeneration on massive hepatectomy using molecular biological method. However, we were not able to elucidate the regulation of liver regeneration using activin, because we had difficulty with the purification of activin. Less
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