缺血型胆道纤维化狭窄大鼠模型的建立  

Establishment of a rat model of extrahepatic biliary ischemic stenosis

作　　者：汪景洲[1] 曾勇[1] 蒋辉[1] 徐缨龙[1] 邱建国[1] 夏天[1] 

机构地区：[1]四川大学华西医院肝胆胰外科,四川省成都市610041

出　　处：《世界华人消化杂志》2011年第4期355-361,共7页World Chinese Journal of Digestology

基　　金：四川省青年科技基金资助项目;No.08ZQ026-091~~

摘　　要：目的:探索建立大鼠缺血型胆道纤维化狭窄动物模型的方法.方法:选取48只成年SD大鼠,随机分为假手术组、胆总管夹闭60、120和180min组共4组,每组12只.假手术组只游离暴露胆总管,其他各组分别用两枚微血管夹夹闭游离的胆总管两端60、120和180min后取出微血管夹,恢复夹闭处胆管的血供.4个实验组分别于术后4wk随机选取8只大鼠行下腔静脉取血,分离血清进行肝功能测定.取胆总管及肝组织石蜡包埋,HE染色,观察组织病理变化并观察各组动物的存活率、体质量改变情况.剩余大鼠于术后8wk处死,行肝功能的测定及组织病理学检查.结果:假手术组、60min组和120min大鼠的存活率为100,180min组大鼠的存活率为75(9/12).术后4wk,60、120和180min组大鼠体质量明显低于较假手术组(240.4g±11.5g,212.7g±13.6g,200.6g±11.8gvs260.6g±15.7g,均P<0.05).各组大鼠肝功能指标存在明显差异,60、120、180min组与假手术组相比显著增高(ALT:55.3IU/L±5.3IU/L,215.6IU/L±26.8IU/L,245.5IU/L±38.5IU/Lvs45.5IU/L±3.9IU/L,均P<0.05;AST:161.3IU/L±15.9IU/L,645.3IU/L±50.5IU/L,698.8IU/L±46.7IU/Lvs140.3IU/L±6.1IU/L,均P<0.05;TILB:8.5μmol/L±1.2μmol/L,72.6μmol/L±11.0μmol/L,78.7μmol/L±12.2μmol/Lvs6.1μmol/L±1.2μmol/L,均P<0.05;ALP:202.4IU/L±20.7IU/L,815.4IU/L±68.1IU/L,902.9IU/L±96.6IU/Lvs158.5IU/L±23.6IU/L,均P<0.05;GGT:10.6IU/L±2.7IU/L,52.3IU/L±8.6IU/L,57.4IU/L±11.3IU/Lvs7.6IU/L±1.4IU/L,均P<0.05);120与60min组相比显著增高;180min与120min相比升高不明显.组织病理检查显示:假手术组、60min组缺血处胆管组织管腔狭窄不明显,管壁纤维化程度较轻.120和180min组缺血处胆管管腔变小,管壁纤维增厚明显,管壁上皮细胞出现坏死脱落,夹闭处以上胆管扩张明显,管壁变薄.术后8wk上述病变不能自行恢复.结论:采用微血管夹钳夹的方法可以建立稳定的大鼠缺血型胆道纤维化狭窄动物模型,为研究肝移植术后胆道的缺血型病变形AIM：To develop a rat model of extrahepatic biliary ischemic stenosis.METHODS：Forty-eight Sprague-Dawley rats were divided randomly and equally into four groups：rats undergoing sham operation and those subjected to clamping of the common bile duct with a clip for 60,120,or 180 min.After scheduled clamping,the clip was removed to recover blood supply.The animals were killed 4 and 8 wk after operation.The survival,liver function,and histopathological changes were observed in rats of each group.RESULTS：The survival rate was 100 in rats undergoing sham operation and those undergoing clamping for 60 or 120min,and 75 in those undergoing clamping for 180 min.At week 4,the body weight of rats undergoing clamping for 60,120 or 180 min was lower than that of rats undergoing sham operation（240.4 g ± 11.5 g,212.7 g ± 13.6 g,200.6 g ± 11.8 g vs 260.6 g ± 15.7 g,all P 0.05）.Liver function parameters were higher in rats undergoing clamping for 60,120 or 180 min than in those undergoing sham operation（ALT：55.3 IU/L ± 5.3 IU/L,215.6 IU/L ± 26.8 IU/L,245.5 IU/L ± 38.5 IU/L vs 45.5 IU/L ± 3.9 IU/L,all P 0.05;AST：161.3 IU/L ± 15.9 IU/L,645.3 IU/L ± 50.5 IU/L,698.8 IU/L ± 46.7 IU/L vs 140.3 IU/L ± 6.1 IU/L,all P 0.05;TILB：8.5 μmol/L ± 1.2 μmol/L,72.6 μmol/L ± 11.0 μmol/L,78.7 μmol/L ± 12.2 μmol/L vs 6.1 μmol/L ± 1.2 μmol/L,all P 0.05;ALP：202.4 IU/L ± 20.7 IU/L,815.4 IU/L ± 68.1 IU/L,902.9 IU/L ± 96.6 IU/L vs 158.5 IU/L ± 23.6 IU/L,all P 0.05;GGT：10.6 IU/L ± 2.7 IU/L,52.3 IU/L ± 8.6 IU/L,57.4 IU/L ± 11.3 IU/L vs 7.6 IU/L ± 1.4 IU/L,all P 0.05）.Histopathological examination showed that biliary stenosis was not apparent and wall f ibrosis was milder in rats undergoing sham operation and those undergoing clamping for 60 min,while severe biliary stenosis and wall fibrosis were observed in those undergoing clamping for 120 or 180 min.At week 8,these lesions could not regress spontaneously.CONCLUSION：An animal model of extrahepatic biliary ischemic stenosis is successfully establish

关 键 词：胆道并发症 缺血型胆道狭窄病变 动物模型 大鼠 

分 类 号：R657.3[医药卫生—外科学] R-332[医药卫生—临床医学]