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Biochemical and electron-microscopic studies on metabolism of the hepatocytes and body during isolated liver perfusion in weanling swine.

断奶猪离体肝脏灌注过程中肝细胞和机体代谢的生化和电镜研究。

基本信息

批准号：
14571701
负责人：
SEO Takehiko
金额：
$ 2.24万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

The present study was designed to investigate metabolic changes in the liver during isolated liver perfusion with double bypass using automatic blood pumps. Isolated liver perfusion was established with bypass between, the hepatic vein and portal vein in 15 weanling Yorkshire swine weighing 8.0 to 12.1 kg with a mean body weight of 9.9 kg, at a flow rate of 20 ml/mm/kg for up to 4 hours. The perfusion circuit was infused with glucose-free 1/2 saline solution at 15 ml/hour, and insulin or glucagon were added. The animals were divided into 5 groups by means of contents of perfusate ; CONT : liver perfusion with perfusate without hormone, 25RI : containing 25 units of regular insulin in 500 ml of perfusate, 75RI : containing 75 units of regular insulin in 500 ml of perfusate, 25GL : containing 0.25 mg of glucagon in 15 ml of perfusate, and 50GL : containing 0.5 mg of glucagon in 15 ml of perfusate.As a result, total protein, albumin, and total cholesterol were gradually decreased with time and there were no differences between the groups. On the contrary, triglyceride was gradually increased with time, and its increase was marked in groups with perfusate containing insulin. Blood glucose was significantly elevated after initiation of liver perfusion, and kept constant thereafter in CONT and glucagons groups. Its elevation was higher in groups with glucagons than in the CONT group. Blood glucose after 2 hours of perfusion was gradually and significantly decreased in groups perfused with perfusate containing insulin. Its decrease was more marked in the 75RI group than in 25 RI group. Insulin influences the hepatic metabolism during isolated perfusion in dose-response manner.We also investigated Iinterleukin-6 (IL-6) and Tumor Necrosis Factor-α (TINE-α) during liver perfusion, and TNF-α, which was thought to be the cause of hyperglycemia, was kept within normal limits during liver perfusion.

本研究旨在研究在使用自动血泵的双转流隔离肝脏灌注过程中肝脏的代谢变化。在15只体重为8.0 - 12.1 kg、平均体重为9.9 kg的断奶约克郡猪的肝静脉和门静脉之间建立了隔离肝灌注，流速为20 ml/mm/kg，持续4小时。灌注回路以15 ml/h的速度输注无葡萄糖的1/2盐水溶液，并加入胰岛素或胰高血糖素。根据灌流液的含量将动物分为5组：CONT：用不含激素的灌流液进行肝脏灌流，25 RI：在500 ml灌流液中含有25单位的常规胰岛素，75 RI：在500 ml灌流液中含有75单位的常规胰岛素，25 GL：在15 ml灌流液中含有0.25 mg胰高血糖素，50 GL：结果，总蛋白、白蛋白和总胆固醇随时间逐渐降低，组间无差异。相反，甘油三酯随着时间的推移而逐渐增加，并且在含胰岛素的灌流液组中其增加显著。CONT组和胰高血糖素组的血糖在肝脏灌流开始后显著升高，此后保持恒定。其升高在胰高血糖素组中高于CONT组。灌流2小时后，血糖逐渐下降，并显着灌流液中含有胰岛素组。75 RI组较25 RI组下降更明显。胰岛素以剂量-反应方式影响离体灌流时肝脏的代谢，同时观察了肝脏灌流过程中IL-6和TINE-α的变化，并观察到TNF-α在肝脏灌流过程中被认为是高血糖的原因。