| Project/Area Number |
03454312
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
OUCHI Kiyoaki Tohoku University School of Medicine, Associate Professor, 医学部, 助教授 (20124555)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Masanori Tohoku University School of Medicine, Assistant, 医学部附属病院, 助手 (70206530)
MATSUBARA Shuji Tohoku University School of Medicine, Assistant Professor, 医学部附属病院, 講師 (20165856)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | liver dysfunction / endotoxin / PCOOH / Kupffer cell / leukocyte / endothelial cell / scavenger / 混合培養 / ラット / Kuptter細胞 |
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| Research Abstract |
The membrane lipid peroxidation of the liver tissue and hepatocytes was studied in order to clarify the pathogenesis of liver dysfunction in endotoxcmia. Phosphatidylcholine hydroperoxide (PCOOH) which is a specific membrane lipid oxidant was measured using high performance liquid chromatography- chemiluminescence technique. Peritonitis was induced in rats by ligation and puncture of the cecum. Blood endotoxin levels were progressively increased until 24 hours after induction of peritonitis. Hepatic PCOOH markedly increased from 740 pmol/mg to 2.628 pmol/mg after 24 hours of peritonitis, and hepatic energy charge reduced from 0.86 to 0.73. In addition, reduction of hepatic energy charge as well as increase of hepatic PCOOH was significantly suppressed by an administration of superoxide dismutase and catalase in rats with peritonitis. As hepatic tissue blood flow showed little changes throughout the experiment, an increased hepatic membranous lipid peroxidation might be one of the main causative factors for the deteriorated hepatic energy metabolism in endotoxemia. The increases of PCOOH of the hepatocytes, as well as GPT in supernatant, were achieved only when endotoxin was added to the co-culture with Kupffer cells, and not to hepatocytes alone. This evidence suggests that Kupffer cells activated by endotoxin may affect membrane lipid peroxidation of the hepatectocytes. Significant contribution of the infiltrating leukocytes and sinusoidal endothelial cells for the pathogenesis of hepatocyte injury in endotoxemia need to be further studies.
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