| Project/Area Number |
12671314
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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 | Kochi Medical School |
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Principal Investigator |
SASAGURI Shiro Kochi Medical School, School of Medicine, Professor, 医学部, 教授 (60196186)
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| Co-Investigator(Kenkyū-buntansha) |
ASAKAI Rei Tokyo Medical and Dental University Medical Research Institute, Research Associate, 難治疾患研究所, 助手 (20167224)
NISHIMORI Hideaki Kochi Medical School, School of Medicine, Research Associate, 医学部, 助手 (70294840)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | mitochondria / PTP / reperfusion injury / myocardial Preservation / アポトーシス / 心機能の保持 / 心筋虚血再灌流傷害 / 細胞死抑制化合物(MS) |
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| Research Abstract |
Introduction
Mitochondrial permeability transition pore (PTP) has been focused due to its essential role of the cell death. The decision between apoptotic and necrotic cell death may rest on the extent of mitochondrial permeability transition. Recently it has been demonstrated that, the novel compound, MS, inhibit cell death similar to bcl-2 by its direct association with PTP. Using this novel compound, we have tried to demonstrate the protective effects of MS compound in reperfusion injury both in vivo and ex vivo.
In vivo Study :
After anethetizing and ventilating, the male wistar rats weighing around 200 g underwent 30 minutes left coronary artery occlusion. TTC and SSDNA staining after 120 minutes reperfusion revealed, less area of myocardial infarction and less prevalence of apoptotic cells, on treatment with MS1, which was completely inhibited by opening the PTP with lonidamine, thus confirming the cytoprotective effect of MS1.
Ex vivo Study :
The hearts from male wistar rats were perfused in the working mode of the Langendorf model. After 30 minutes of perfusion, the hearts were arrested with St. Thomas cardioplegic solution and was preserved in the preservative solutions with or without MS1. 60 minutes reperfusion following 12 hrs preservation revealed significant recovery of Cardiac functions, well maintained myocardial ATP, less tissue water content and well preserved mitochondria in the MS1 preserved group. Again this effect of MS1 has been completely inhibited on pretreating the rats with the PTP opener lonidamine thus demonstrating the protective effect of this compound.
Conclusion
Our results have demonstrated the cytoprotective effect of MS1 in preventing the myocardial damage both invivo and exvivo and would be a promising drug in preventing the myocardium in near future.
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