| Project/Area Number |
63440033
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Department of Internal Medicine, School of Medicine, Keio University |
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Principal Investigator |
TSUCHIYA Masaharu MD Professor, 医学部・消化器内科, 教授 (60051124)
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| Co-Investigator(Kenkyū-buntansha) |
SUEMATSU Makoto Instructor, 医学部・消化器内科, 助手 (00206385)
MIURA Soichiro Associate Professor, 医学部・消化器内科, 講師 (50138012)
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| Project Period (FY) |
1988 – 1990
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| Keywords | oxygen radicals / digital imaging / photonic intensifier / microcirculation / chemiluminescence / dichlorofluorescin diacetate / ischemia / oxidative stress |
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| Research Abstract |
This project was aimed to establish the methodology to investigate microtopography of oxygen radical formation in microcirculatory units. Recent development of digital imaging photonic microscopy has made it possible to analyze spatial and temporal alterations of oxyradical generation during tissue injury. Luminol-dependent photonic imaging revealed granulocyte-mediated oxidative stress during microvascular damage induced by platelet-activating factor or endotoxin. Our data also demonstrated that the interface between venular indothelium and sticking granulocytes may be the most critical site of oxidant-dependent cellular damage. We have developed another new method to visualize intracellular oxidative stress in the isolated perfused rat liver using digital imaging microfluorography and a hydroperoxide-sensitive fluorescence dye, dichlorofluorescin diacetate. In the experimental model of carbon tetrachloride-induced hepatic injury, the method has revealed that cytochrome P450-dependent oxidant formation takes place predominantly in pericentral regions, preceding cell death at the same area. The current technique will provide a useful method to investigate the microtopograp hy of organ microcirculatory oxidative stress associated with xenobiotic metabolism or circulatory failure.
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