| Project/Area Number |
18590509
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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 |
Applied pharmacology
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| Research Institution | Okayama University |
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Principal Investigator |
TAKAHASHI Hideo Okayama University, Grad. Sch. of Med. Dent. and Pharm. Sci, Assist.Prof (60335627)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIBORI Masahiro Okayama Univ, Grad. Sch. of Med Dent. and Pharm. Sci, Prof (50135943)
KANKE Toru Okayama Univ, Grad. Sch. of Med Dent. and Pharm. Sci, Asses. Prof (50432638)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | neucleokine / counteract antibody / coronary ischemia / monocyte / macronharee / brain ischemia / infarction / inflammation / vessel spas |
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| Research Abstract |
Background
Coronary ischemia-reperfusion (I/R) injury proceeds to cause cardiomyocyte necrosis. The pathogenesis of I./R injury is a multi-step process including an inflammatory reaction. A recent study has suggested that high-mobility group boxl (HMGB1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. A neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB1 in cardiac I/R injury. Methods and results
Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. Rats were administered an intravenous injection of anti-HMGB1 mAb or control IgG just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison to the control group (p<0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin T (TpT) and norepinephrine (NE) content in the heart in comparison to the control (p<0.05). Moreover, the production of DHPG was reduced in the anti-HMGB1-treated group (p<0.05).
Conclusion
This study showed for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in rat heart. These findings supported the novel view that I/R-induced HMGB1 may be an important factor to modulate interstitial NE.
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