Bile duct ligature in young rats: A revisited animal model for biliary atresia

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Matias Garrido
Camila Escobar
Constanza Zamora
Carolina Rejas
Juan Varas
Mario Párraga
Sebastian San Martin *
Sandra Montedónico
(*) Corresponding Author:
Sebastian San Martin | sebastian.sanmartin@uv.cl

Abstract

Biliary atresia leads to cirrhosis in the vast majority of patients and constitutes the first cause of paediatric liver transplantation. Animal models allow us to understand the molecular basis and natural history of diseases. The aim of this study is to describe a surgically created animal model of biliary atresia with emphasis in long-term liver function. Forty-two 3-week-old Sprague-Dawley rats were randomly divided into two groups: bile duct ligature (BDL) and control. The animals were sacrificed on the 2nd, 4th, and 6th postoperative weeks. Blood samples were collected for liver function analysis. The spleen to body weight ratio was determined. Histopathological examination of liver tissue was performed by hematoxylin-eosin and Sirius red staining. Collagen quantification was determined by using colorimetric digital image analysis and was expressed as a percentage of total liver tissue area. Quantitative real-time polymerase chain reaction was performed to analyse gene expression levels of transforming growth factor-β1 (Tgfb1) and apeline (Apln) genes. Statistical analysis was performed where P<0.05 was considered significant. Animals from BDL group developed increasing cholestasis with clinical and laboratory features. Splenomegaly was detected at 4th and 6th week (P<0.05). Histological evaluation of the liver showed ductular reaction, portal fibrosis and bile plugs. Collagen area to total liver tissue area had a median of 2.5% in the control group and 6.5 %, 14.3 % and 37.7 % in BDL rats at 2nd, 4th and 6th weeks respectively (P<0.001). Tgfb1 mRNA expression level was significantly higher at 6th week (P<0.001) in BDL group when compared to control. Apln mRNA expression level was significantly higher at 4th and 6th week (P<0.001) and showed a positive linear correlation (r = 0.975, P<0.05) in BDL group when compared to control. Bile duct ligature in young rats is an animal model that recreates clinical, laboratory, histological and molecular findings of biliary atresia. Bile duct ligature constitutes a good animal model to investigate therapeutic approaches for modifying the progression of liver fibrosis in biliary atresia.


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