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Pathogenesis of hepatic injury in endotoxemia: with special reference to phosphatidylcholine hydroperoxide accumulation

内毒素血症肝损伤的发病机制：特别涉及氢过氧化磷脂酰胆碱的积累

基本信息

批准号：
03454312
负责人：
OUCHI Kiyoaki
金额：
$ 4.29万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454312/
关键词：
liver dysfunction endotoxin PCOOH Kupffer cell leukocyte endothelial cell scavenger 混合培養ラット Kuptter細胞

项目摘要

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.

为阐明内毒素血症时肝功能损害的发病机制，对肝组织和肝细胞膜脂质过氧化进行了研究。采用高效液相色谱-化学发光法测定了膜脂特异性氧化剂过氧化磷脂酰胆碱（PCOH）的含量。通过结扎和穿刺盲肠在大鼠中诱导腹膜炎。血液内毒素水平逐渐升高，直至诱导腹膜炎后24小时。腹膜炎24小时后，肝脏PCOH从740 pmol/mg显著增加至2.628 pmol/mg，肝脏能荷从0.86降低至0.73。此外，在腹膜炎大鼠中，超氧化物歧化酶和过氧化氢酶的给药显著抑制了肝脏能荷的减少以及肝脏PCOH的增加。由于肝组织血流量在整个实验过程中变化不大，肝细胞膜脂质过氧化反应增强可能是内毒素血症时肝脏能量代谢恶化的主要原因之一。肝细胞的PCOOH以及上清液中的GPT的增加仅在将内毒素加入到与枯否细胞的共培养物中时实现，而不是单独的肝细胞。提示内毒素激活枯否细胞可能影响肝细胞膜脂质过氧化反应。浸润的白细胞和肝窦内皮细胞在内毒素血症肝细胞损伤的发病机制中的重要作用有待进一步研究。