Role of hepatic arterial ischaemia in biliary fibrosis following liver transplantation  

作　　者：LU Hong-wei CHEN Yong-bing LI Yi-ming DONG Jia-hong YANG Hui-ning 

机构地区：[1]Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China [2]Department of Hepatobiliary Surgery, Beijing Military Region General Hospital, Beijing 100700, China [3]Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China [4]Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China [5]Department of Nosocomial Infection Management and Disease Control, Armed Police General Hospital, Beijing 100039, China

出　　处：《Chinese Medical Journal》2010年第7期907-911,共5页中华医学杂志（英文版）

基　　金：This study was supported by a grant from the National Natural Science Foundation of China （No. 30571765 ）.Acknowledgements： We thank Mr. JI Hong and Mr. XU Jin-kai （Department of General Surgery, Second Affiliated Hospital of Medical College, Xi＇an Jiaotong University） for skillful technical assistance.

摘　　要：Background In clinical liver transplantation, whether the delay of hepatic arterial ischaemia increases biliary fibrosis or not is controversial. We designed a liver transplantation model to test this controversy and explore its mechanism. Methods Twelve dogs were divided into two groups randomly： hepatic arterial ischaemia （HAI） and control groups. In HAI group, hepatic artery was perfused 60 minutes after portal perfusion, but in control group, hepatic arterial perfusion was simultaneous with portal perfusion. The pathological changes of intrahepatic bile ducts were observed. Transforming growth factor beta 1 （TGF-β1）, expressed in epithelial cells of intrahepatic bile duct, was detected by immunohistochemical streptoadividin-biotin complex method. Expressions of Smad3, P-Smad3 and the transcriptional levels of alpha smooth muscle actin （α-SMA） mRNA in intrahepatic bile ducts were detected by Western blotting and RT-PCR respectively.Results Compared with the control group, more collagen deposition and leucocytic infiltration could be seen in biliary vessel walls. Significantly more buffy particles, which are the proteins of TGF-β1, could be seen in biliary epithelial cells. P-Smad3 and α-SMA mRNA （as ratio to corresponding β-actin） in intrahepatic bile ducts were 1.82±0.18 and 1.86±0.73 respectively in HAI group, significantly higher than those in control group （0.59±0.09 and 0.46±0.18, respectively）. Conclusions Hepatic arterial ischaemia could increase the deposition of collagen fibres, trigger the transdifferentiation of myofibroblasts in intrahepatic bile duct and might result in biliary fibrosis by activating the TGF-β1 signalling pathway.Background In clinical liver transplantation, whether the delay of hepatic arterial ischaemia increases biliary fibrosis or not is controversial. We designed a liver transplantation model to test this controversy and explore its mechanism. Methods Twelve dogs were divided into two groups randomly： hepatic arterial ischaemia （HAI） and control groups. In HAI group, hepatic artery was perfused 60 minutes after portal perfusion, but in control group, hepatic arterial perfusion was simultaneous with portal perfusion. The pathological changes of intrahepatic bile ducts were observed. Transforming growth factor beta 1 （TGF-β1）, expressed in epithelial cells of intrahepatic bile duct, was detected by immunohistochemical streptoadividin-biotin complex method. Expressions of Smad3, P-Smad3 and the transcriptional levels of alpha smooth muscle actin （α-SMA） mRNA in intrahepatic bile ducts were detected by Western blotting and RT-PCR respectively.Results Compared with the control group, more collagen deposition and leucocytic infiltration could be seen in biliary vessel walls. Significantly more buffy particles, which are the proteins of TGF-β1, could be seen in biliary epithelial cells. P-Smad3 and α-SMA mRNA （as ratio to corresponding β-actin） in intrahepatic bile ducts were 1.82±0.18 and 1.86±0.73 respectively in HAI group, significantly higher than those in control group （0.59±0.09 and 0.46±0.18, respectively）. Conclusions Hepatic arterial ischaemia could increase the deposition of collagen fibres, trigger the transdifferentiation of myofibroblasts in intrahepatic bile duct and might result in biliary fibrosis by activating the TGF-β1 signalling pathway.

关 键 词：liver transplantation biliary fibrosis hepatic arterial ischaemia transforming growth factor-beta 1 

分 类 号：R686[医药卫生—骨科学]