2001 Fiscal Year Final Research Report Summary
ESTABLISHMENT OF NEW IMMUNOSUPPRESSIVE STRATEGY USING GENE TRANSFECTION TECHNIQUE
| Project/Area Number |
12470274
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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 |
Thoracic surgery
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
FUKUSHIMA Norihide Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Motonobu Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90291442)
SAWA Yoshiki Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00243220)
OHTAKE Shigeaki Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (50243209)
MATSUMIYA Goro Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20314312)
KAGISAKI Koji Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30335351)
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| Project Period (FY) |
2000 – 2001
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| Keywords | HEART TRANSPLANATION / GENE TRANSFECTION / END-STAGE CARDIAC FAILURE / nFkB DECOY / ORGAN PRESERVATION / HVJ-LIPOSOME METHOD / ISCHEMIA-REPERFSION INJURY |
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| Research Abstract |
BACKGROUND : Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischernia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function.
METHODS : Double-stranded oligodeoxynucleotides with a specific affinity for NFkappaB (NFkappaB decoy group) or a "rambled decoy group were transfected into rat hearts using a hemagglutinating virus ofjapan-liposome method. After 16 "urs of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanatestaining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue 1L-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS : Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.
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