Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||TOHOKU UNIVERSITY|
ORII Takashi Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (20282048)
ANDO Kenjiro Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (40261614)
DOI Hideyuki Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (90188839)
OHKOHCHI Nobuhiro Graduate Sch. of Medicine, Tohoku Univ., Associate Prof., 大学院・医学系研究科, 助教授 (40213673)
CHUBACHI Seiji Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (90302108)
SEKIGUCHI Satoshi Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (20312580)
桜田 正寿 東北大学, 医学部附属病院, 助手 (40292320)
|Project Period (FY)
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,200,000 (Direct Cost : ¥2,200,000)
|Keywords||Liver transplantation / Fatty liver / Fatty liver model of rat / mitochondrial ATP / Injury of sinusoidal lining cells / リポゾーム封入クロドロネート / 肝脂肪 / ミトコンドリア ATP産生態|
1. Making an animal model
As a rat model with a moderately (30〜60%) fatty liver, we could make it nearly equal to human fatty liver by feeding the rat with cholesterol-rich meal.
2. Examination of mitochondrial ATP synthesis
Compared fatty liver model (F-model) to normal model (N-model) about liver tissue ATP, energy charge, and the activity of proton ATPase, there were no significant differences among them.
3. Examination of injury of sinusoidal lining cells (SLCs)
To clarify injury of SLCs, we measured hyaluronic acid (HA) of blood and compared it in F-model to it in N-model. HA in F-model was significantly higher than in N-model, so it was suggested that SLCs of F-model was more fragile than those of N-model.
4. Results of liver transplantation
Whole fatty liver was resected and was stored in cold UW solution for 1, 6, 12 hours. After storage, we transplanted the graft orthotopically and compared survival rate of rat with fatty liver graft to that with normal liver graft. While all of the recipients with normal liver grafts survived for more than one week, survival rate at one week of recipients with fatty liver grafts stored in 6 hours was 40% and that in 12 hours was 0%. Mitochondrial ability of ATP synthesis after 6 hour-storage was not significantly different between fatty and normal liver graft, but after repurfusion the injury of SLCs of fatty liver graft was severer than that of normal graft.
5. Preparation of drugs for preventing reperfusion injury
(1) To eliminate Kuppfer cells which strongly affected repurfusion injury, L-DMDP was pretreated in donors, and (2) to inhibit PLAィイD22ィエD2 activity at repurfusion, liver graft was rinsed with Nafamostat mesilate (NM) rinse solution. However, the rats with fatty liver grafts were not improved to survive by preparation of either drug.