Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats
Autor: | Barbara Barbaro, Yoshiyuki Ueno, Ramona Reichenbach, Shannon Glaser, Marco Marzioni, Domenico Alvaro, Eugenio Gaudio, Antonio Franchitto, Heather Francis, Gianfranco Alpini, Giammarco Fava, Ryun Summers, Paolo Onori, Julie Venter |
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Rok vydání: | 2006 |
Předmět: |
Male
Vascular Endothelial Growth Factor A ductal secretion mitosis camp intrahepatic biliary epithelium secretin microcirculation medicine.medical_specialty Physiology Cholangiocyte proliferation Intrahepatic bile ducts digestive system Cholangiocyte Microcirculation Hepatic Artery Cholestasis Fibrosis Physiology (medical) Internal medicine medicine Animals Ligation Hepatology Bile duct business.industry Gastroenterology medicine.disease Rats Inbred F344 Rats Disease Models Animal Treatment Outcome medicine.anatomical_structure Endocrinology Liver Bile Ducts business |
Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 291:G307-G317 |
ISSN: | 1522-1547 0193-1857 |
DOI: | 10.1152/ajpgi.00507.2005 |
Popis: | The hepatic artery, through the peribiliary plexus, nourishes the intrahepatic biliary tree. During obstructive cholestasis, the nutritional demands of intrahepatic bile ducts are increased as a consequence of enhanced proliferation; in fact, the peribiliary plexus (PBP) displays adaptive expansion. The effects of hepatic artery ligation (HAL) on cholangiocyte functions during cholestasis are unknown, although ischemic lesions of the biliary tree complicate the course of transplanted livers and are encountered in cholangiopathies. We evaluated the effects of HAL on cholangiocyte functions in experimental cholestasis induced by bile duct ligation (BDL). By using BDL and BDL + HAL rats or BDL + HAL rats treated with recombinant-vascular endothelial growth factor-A (r-VEGF-A) for 1 wk, we evaluated liver morphology, the degree of portal inflammation and periductular fibrosis, microcirculation, cholangiocyte apoptosis, proliferation, and secretion. Microcirculation was evaluated using a scanning electron microscopy vascular corrosion cast technique. HAL induced in BDL rats 1) the disappearance of the PBP, 2) increased apoptosis and impaired cholangiocyte proliferation and secretin-stimulated ductal secretion, and 3) decreased cholangiocyte VEGF secretion. The effects of HAL on the PBP and cholangiocyte functions were prevented by r-VEGF-A, which, by maintaining the integrity of the PBP and cholangiocyte proliferation, prevents damage of bile ducts following ischemic injury. |
Databáze: | OpenAIRE |
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