Gene therapy in lung transplantation. Attenuation of ischemia/reperfusion injury and acute rejection by NF-kB decoy transfection
| Project/Area Number |
12671307
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
MINAMI Masato Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10240847)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Meinoshin Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40252647)
OHTA Mitsunori Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30203805)
武田 伸一 大阪大学, 医学系研究科, 助手 (30236468)
三好 新一郎 大阪大学, 医学系研究科, 助教授 (00190827)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | rat lung transplantation / nitric oxide / acute rejection / NF-kB / decoy / transfection / HVJ liposome / lung injury / NFKB / 肺移植 / 肺傷害 / NFkB / HVJ-liposome法 |
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| Research Abstract |
This study are to determine whether NF-kB decoy transfection into the allograft during harvest reduce nitric oxide (NO) production and ameliorate acute lung rejection. Left lung transplantation was performed using pairs of Brown Norway(RT1n) and Lewis (RT1I) rats. All allografts were flushed with PBS solution 20 ml containing hemaglutinating virus of Japan (HVJ) liposome-ODNs complex of NF-kB decoy (n=6) and preserved for 60 minutes at 4℃, Scrambled decoy was regarded as control (n=5) as well as simple PBS solution (n=5). Five days after transplantation without use of immunosuppressants, exhaled NO, gas exchange and histological rejection score of the graft were determined. Exhaled NO level significantly reduced in group with NF-kB decoy transfection compared with control (445±162 vs. 1305±123 ppb, p<0.02) as well as improvement in PaO2 (197±28 vs. 60±18 mmHg, p<0.02) and rejection score (1.6±0.4 vs. 2.5±0.4). Inhibition of NF-kB activation in the allograft by ODNs decoy transfection into the donor lung ameliorated lung injury in acute allograft rejection. This result implies a possible therapeutic target for allo-independent pathway, which seemed to be feasible in conjunction with immuinosuppression in the clinical setting of lung transplantation.
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Report
(3 results)
Research Products
(5 results)
