Project/Area Number |
13671558
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
|
Research Institution | HOKKAIDO UNIVERSITY |
Principal Investigator |
MATSUDA Naoyuki HOKKAIDO UNIVERSITY, Hokkaido Univ., Grad. School of Med., Instructor (50332466)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | Sepsis / Shock / G protein / Gene Therapy / NF-KB / Gsタンパク / NF-κβ / 心室筋 |
Research Abstract |
We used the rabbits and mice, which rendered sepsis by LPS injection or cecum ligation and puncture. Decreased expression of Gs α were reversed by steroid and by the gene therapy which used NF-kB decoy oligonucleotides (ODN) for the inhibition of transcriptional activity of NF-kB DNA region. In addition, we found radical scavenger could inhibit decreased expression of Gs α in septic rabbits. By these study process, high efficiency of transfection of NF-kB decoy oligonucleatides were found in lungs and atrial muscle. Depended on NF-kB activity in atrial muscle, histamine plasma concentration, expressions of histamine receptor H_1 receptor and H_2 receptor found possibility to rise in sepsis shock. By a gene therapy of a NF-kB DON, we could completely restrain gene transcription of H_2 receptor and L-histidine decarboxylase in the atrium of septic rabbits In addition, we merged acute lung injury for sepsis. Induction of a NF-kB decoy ODN may be available for new treatment of septic shock
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