移植肝胆汁成分失衡与胆管损伤关系的实验研究

摘要

目的 探讨移植肝术后早期胆汁主要成分的变化规律及其在胆管损伤中的意义.方法 大鼠被随机分为对照组(A组)、供肝冷保存1h组(B组)和供肝冷保存12h组(C组),移植组均采用动脉化的大鼠肝移植胆道外引流模型.术后按1、3、5、7、10和14d共6个时相点采集标本并进行相关生化及病理学指标的检测.结果 冷保存/再灌注损伤对大鼠移植肝胆汁主要成分有显著影响.术后14 d内胆盐分泌恢复的速度明显高于磷脂分泌恢复的速度,使得在术后1～14 d的时间内,胆盐与磷脂的分泌量之比为正常水平的2～5倍,并且供肝冷保存时间呈正相关;进一步分析提示移植肝胆盐分泌量与γ-谷氨酰转肽酶、碱性磷酸酶分泌量及胆管受损程度显著相关.结论 冷保存/再灌注损伤可以导致移植肝胆汁成分失衡,在移植肝胆管损伤的发生发展中可能具有一定作用.%Objective To investigate the change of bile composition and its role in bile duct injury after othrotopic liver transplantation(OLT).Methods Rats were randomly divided into 3 groups:group A(sham surgery),group B(OLT with 1 h cold preservation),group C(OLT with 12 h cold preservation).The arterialized rat liver transplantation model with biliary extra-drainage was used in group B and C.Animals were sacrificed at posttransplant 1,3,5,7,10 and 14 day.Routine bile chemistry and pathological assays were performed.Results Cold preservation/reperfusion injury(CPRI)could repress the secretion of bile salts and phospholipid.However,in contrast with a rapid increase of bile salt secretion,the biliary secretion of phospholipid recovered more slowly,leading to an abnormal high bile salts/phospholipid ratio early after transplantation.Further analysis suggested that the secretion of bile salts correlated strongly with biochemical and histopathological signs of bile duct injury.Condusions CPRI can lead to great changes of graft bile composition,which plays a role in the pathogenesis of bile duct injury following liver transplantation.