Role of hepatic arterial ischaemia in biliary fibrosis following liver transplantation.
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-beta1), 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 (alpha-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-beta1, could be seen in biliary epithelial cells. P-Smad3 and alpha-SMA mRNA (as ratio to corresponding beta-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-beta1 signalling pathway.
Lu
Hong-Wei
HW
Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Chen
Yong-Bing
YB
Li
Yi-Ming
YM
Dong
Jia-Hong
JH
Yang
Hui-Ning
HN
D000199:Actins / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D006499:Hepatic Artery; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications* / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1