- 作者：Gianluca Svegliati-Baroni ; Roberto Ghiselli ; Marco Marzioni ; Domenico Alvaro ; Federico Mocchegiani ; Stefania Saccomanno ; Valerio Sisti ; Laura Ugili ; Fiorenza Orlando ; Gianfranco Alpini et al.
- 刊名：Journal of Hepatology
- 出版年：2006
- 出版时间：June 2006
- 年：2006
- 卷：44
- 期：6
- 页码：1158-1166
- 全文大小：643 K
Background/Aims
Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats.Methods
After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17β-estradiol or a control solution.
Results
Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17β-estradiol significantly reduced cholangiocyte apoptosis. 17β-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17β-estradiol.
Conclusions
This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17β-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.