Antiapoptotic compound to enhance hypothermic liver preservation.
Antiapoptotic compound to enhance hypothermic liver preservation.
复制标题
抗凋亡化合物可增强低温肝脏保存。
DOI：
10.1097/00007890-199703270-00003
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Chien,S
中科院分区：
文献类型：
--
作者：
Wu,G;Tomei,LD;Bathurst,IC;Zhang,F;Hong,CB;Issel,CJ;Columbano,A;Salley,RK;Chien,S
背景：细胞凋亡(程序性细胞死亡)是移植前隔离和储存过程中器官整体缺血的结果。如果在缺血期间细胞凋亡受到抑制，则应改善器官保存，并可能增加允许保存的时间。本研究的目的是测试一种新开发的抗凋亡化合物LXR-015在延长低温肝脏保存期间的效果。方法：三组大鼠，每组12只。在正常组，采集后立即进行肝功能检查。实验组用含LXR015的Euro-Collins液(30ml/kg体重)冲洗肝脏，浓度相当于9 mg/kg动物体重(300μg/ml)。然后将肝脏在4℃下保存24小时，然后进行肝功能研究。在对照组中，采集的肝脏用不含LXR-015的Euro-Collins液冲洗，然后在4℃下保存24小时，然后进行肝功能检查。结果：正常组和研究组的门静脉血流量高于对照组(P<；0.05)。门静脉阻力正常组和研究组均低于对照组(P<；0.05)。肝组织耗氧量研究组明显高于正常组和对照组(P<；0.05)。对照组肝酶产量(天冬氨酸氨基转移酶、丙氨酸氨基转移酶、乳酸脱氢酶、肌酸激酶)高于研究组和正常组(P<；0.05)。正常组和研究组的胆汁产量均高于对照组(P<；0.05)。正常组和模型组大鼠肝组织湿/干重比均低于对照组(P<；0.05)。组织病理学检查显示，正常组(1.70±0.15个/高倍视野)和研究组(2.08±0.10个/高倍视野)的凋亡小体数(P<；0.05)均少于对照组(7.92±0.15)。结论：与单独使用Euro-Collins液相比，在Euro-Collins液中添加抗细胞凋亡化合物LXR-015显著改善了大鼠肝脏的低温保存。
Background.Apoptosis (programmed cell death) occurs as a consequence of global organ ischemia during isolation and storage prior to transplantation. If apoptosis is inhibited during ischemia, organ preservation should be improved, and the length of time for permissible storage may be increased. The objective of this study was to test the effect of a newly developed antiapoptotic compound, LXR-015, during extended hypothermic liver preservation.Methods.Three groups of 12 rats each were studied. In the normal group, liver function was studied immediately after harvesting. In the study group, harvested livers were flushed with Euro-Collins solution (30 ml/kg body weight) containing LXR-015 at a concentration equivalent to 9 mg/kg animal body weight (300 μg/ml). The livers were then stored at 4 C for 24 hr before liver function was studied. In the control group, harvested livers were flushed with Euro-Collins solution without LXR-015 and then stored at 4 C for 24 hr before liver function was studied.Results.Portal venous flow was higher (P< 0.05) in the normal and study groups compared with the control group. Portal venous resistance was lower (P< 0.05) in the normal and study groups compared with the control group. Liver tissue oxygen consumption in the study group was significantly higher than in both the normal and control groups (P< 0.05). Liver enzyme production (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase) was higher in the control group than in either the study or normal group (P< 0.05). Bile production in both the normal and study groups was higher than in the control group (P< 0.05). The liver tissue wet to dry weight ratio in both the normal and study groups was lower than in the control group (P< 0.05). Histopathology studies revealed fewer apoptotic bodies (P< 0.05) in both the normal (1.70±0.15 per high-power field) and study groups (2.08±0.10 per high-power field) than in the control group (7.92±. 33 per high-power field).Conclusions.Adding an antiapoptotic compound, LXR-015, to Euro-Collins solution significantly improves hypothermic preservation of the rat liver compared with Euro-Collins solution alone.