Project/Area Number |
11671178
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | Nara Medical-University |
Principal Investigator |
HISANAGA Michiyoshi Nara Medical Univ, Facurty of Medicine, Associate Professor., 医学部, 講師 (30275341)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Yoshiyuki Nara Medical Univ, Facurty of Medicine, Professor, 医学部, 教授 (00142381)
澤田 秀智 奈良県立医科大学, 医学部, 講師 (10206021)
|
Project Period (FY) |
1999 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
Keywords | Lirer / Ischemic injury / NF-KB / I-KB / Adeno virus / gene transfection / 異所性心移植 / 拒絶反応 / HVJ-リポゾーム |
Research Abstract |
Nuclear factor-kappa B (NF-kB) regulates various inflammatory cytokines, adhesion molecules, chemokines as well as growth factors that play important roles in organ transplantation. In this study, we planned to induce post transplantation tolerance by controlling NF-kB activation using rat cardiac allo-transplantation model. "Decoy oligodeoxynucleotides", which shares the same kB sequences in nuclear NF-kB binding site, was transected into donor heart as well as recipient using HVJ-liposome. However, transfection was not successful by X-Gal staining, although a lot of trials were attempted. Then we have changed strategies targeting different organs and animal species, I.e., human I-kB adenovirus using CMV promoter (AdCMVhIkB) was transected into mouse liver using hepatic ischemia-reperfusion model. 48 hours before hepaticischemia, 1x10^9 pfu AdCMVhIkB was intraportally injected. Suppression of NF-kB activation as well as I-kB over expression was recognized before ischemia however, significant protective effect was not found so far. Furtherinvestigations concerning dministration sites, timing, and vector numbers are necessary.
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