| Project/Area Number |
09470257
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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 |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KITAJIMA Masaki Keio University, School of Medicine Professor, 医学部, 教授 (90112672)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Nobuyoshi Keio University, School of Medicine Professor, 医学部, 教授 (50162706)
MATSUMOTO Kenji Keio University, School of Medicine Assistant Professor, 医学部, 助手 (20129662)
WAKABAYASHI Go Keio University, School of Medicine Assistant Professor, 医学部, 助手 (50175064)
SHIMAZU Motohide Keio University, School of Medicine Assistant Professor, 医学部, 講師 (70124948)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1998: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1997: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | IL-1Ra / Ischemia-reperfusion injury / Liver transplantation / Gene therapy / Adenoviral vector / Lipofection / in vivo gene delivery / cytokine / IL-1Rg / 肝移植 / サイトカイン / アデノウイルスベクター / 部分肝移植 |
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| Research Abstract |
We have recently reported that an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1Ra) reduces hepatic ischemia-reperfusion injury. The aim of this study is to investigate the effect of the IL-1Ra gene delivery into the rat liver on hepatic ischermia-reperfusion injury. The IL-1Ra cDNAs were delivered into the rat liver in vivo by the aid of plasmid/cationic liposome (lipofection) or recombinant adenoviral vector. Expression of the delivered gene was evaluated by histochemistry or by measuring the concentration of human IL-1Ra protein in rat serum by ELISA.The protective effect of IL-1Ra gene delivery on the hepatic ischemia-reperfusion injury was then evaluated by comparing serum ALT/AST and rat IL-6 or TNF levels and subsequent 7 days survival rate between IL-1Ra gene- and LacZ reporter gene-delivered groups. Our results demonstrated that 24 hours after gene delivery, serum IL-1Ra protein concentration was significantly elevated. Furthermore, 3 hours after hepatic ischemia-reperfusion, serum ALT/AST and rat TNF levels were significantly reduced and the survival rate was significantly higher in the IL-1Ra delivered group as compared with control group. Successful IL-1Ra gene delivery into the liver may be applicable to reduce the rejection after liver transplantation as well as hepatic isehemia-reperfusion injury.
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