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EXPERIMENTAL STUDIES ON AUXILIARY LIVER TRANSPLANTATION BASED ON REDOX THEORY

基于氧化还原理论的辅助肝移植实验研究

基本信息

批准号：
05671099
负责人：
KAMIYAMA Yasuo
金额：
$ 1.28万
依托单位：
KANSAI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671099/
关键词：
Liver failure Liver ischemia Liver transplantation Energy metabolism Redox state Auxiliary liver Liver support Hepatic coma 異所性肝移植ケトン体比ブタ

项目摘要

1. Establishment of biochemical assays of porcine blood ketone bodies. In this study, it is essential to measure the changes in blood ketone body ratio (acetoacetate/b-hydroxybutyrate, KBR) in both arterial blood of the pigs with failed liver and hepatic vein of the auxiliary transplanted liver. We have found that arterial ketone bodies of th pigs are lower than those of men, rabbits, or rats.2. Partial hepatectomy model as a recipient. Initialy, we have tried to establish a liver failure model in 90% hepatectomized pig. However, a hemodynamically stable model could not be made mainly due to large blood loss. Auxiliary liver transplantation in this model resulted in decrease of KBR in both recipient and auxiliary liver. In this model, we have failed to evaluate the availability of KBR as an index of graft failure.3. Establishment of acute liver failure induced by liver ischemia in pigs with portacaval shunt. Acute liver failure was made by the clamping of the hepatic triads for 6 hours. During liver ischemia, the levels of transaminases, arterial ammonia, and potassium were increased gradually. PT and PTT were prolonged. During the hepatic triads clamping, the arterial ketone bodies were hardly detected. Within 2 hours after the declamping, arterial KBR was recovered temporally, but the ratio continued to decline. All pigs died within 8 hours after the declamping. It was suggested that by measuring the changes in arterial KBR in this model, the efficiency of metabolic support as provided by ex-vivo perfused liver or auxiliary transplanted liver could be assessed.4. Since auxiliary liver transplantation on this animal was found to be possible without large blood loss, we have begun to evaluate the availability of KBR as an index of graft failure in this model.

1.猪血酮体生化分析方法的建立在本研究中，有必要测定肝衰竭猪动脉血和辅助性肝移植肝静脉血中血酮体比值(乙酰乙酸酯/b-羟丁酸，KBR)的变化。我们发现猪的动脉血酮体低于人、兔和大鼠。以肝部分切除模型为受体。我们初步建立了90%肝切除猪的肝功能衰竭模型。然而，由于失血过多，无法建立血流动力学稳定的模型。在该模型中，辅助性肝移植使受体和辅助性肝的KBR均降低。在这个模型中，我们没有评估KBR作为移植物失败的一个指标的有效性。门腔分流术猪肝缺血型急性肝功能衰竭模型的建立。夹闭肝三联模型6h，造成急性肝功能衰竭。肝脏缺血时，转氨酶、血氨、血钾水平逐渐升高。PT、PTT延长。肝三联夹闭过程中，动脉酮体几乎未检出。开放后2小时内，动脉KBR暂时恢复，但比率继续下降。所有猪在断奶后8小时内死亡。提示在该模型中，通过测量动脉血KBR的变化，可以评估体外灌流肝或辅助性移植肝提供代谢支持的效率。由于在该动物上的辅助性肝移植被发现是可能的而不需要大量失血，我们已经开始评估KBR作为该模型中移植物失败的一个指标的可用性。