Chronic Portal Hypertension in the Rat by Triple-Portal Stenosing Ligation

Diéguez, B; Aller, María-Ángeles; Nava, María-Paz; Palma, Maria Dolores; Árias, Jorge L.; López, Laudino; Árias, Jaime

doi:10.1080/08941930290086146

Cited by 35 publications

(30 citation statements)

References 22 publications

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“…It is possible that the pancreatic phenotype in mice reflects some species variation because this presentation differs from human ARPKD and the pck rat model, in which kidney and liver phenotypes predominate and the pancreas does not appear to be affected. 23 The presence of splenomegaly in a large percentage of the mice may be secondary to portal hypertension, 34,35 which is commonly associated with hepatic fibrosis and is a clinical manifestation of older patients with ARPKD. 5 Extrahepatic bile duct dilatation was seen in more than 25% of the mice studied but increased in prevalence to ϳ40% in mice 9 months of age and older.…”

Section: Discussionmentioning

confidence: 99%

Biliary and Pancreatic Dysgenesis in Mice Harboring a Mutation in Pkhd1

Gallagher

Esquivel

Briere

et al. 2008

The American Journal of Pathology

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Autosomal recessive polycystic kidney disease is a hereditary fibrocystic disease that involves the kidneys and the biliary tract. Mutations in the PKHD1 gene are responsible for typical forms of autosomal recessive polycystic kidney disease. We have generated a mouse model with targeted mutation of Pkhd1 by disrupting exon 4, resulting in a mutant transcript with deletion of 66 codons and expression at ϳ30% of wild-type levels. Pkhd1 del4/del4 mice develop intrahepatic bile duct proliferation with progressive cyst formation and associated periportal fibrosis. In addition, these mice exhibit extrahepatic manifestations, including pancreatic cysts, splenomegaly, and common bile duct dilation. The kidneys are unaffected both histologically and functionally. Fibrocystin is expressed in the apical membranes and cilia of bile ducts and distal nephron segments but is absent from the proximal tubule. This pattern is unchanged in orthologous models of autosomal dominant polycystic kidney disease due to mutation in Pkd1 or Pkd2. Mutant fibrocystin in Pkhd1 del4/del4 mice also retains this expression pattern. The hypomorphic Pkhd1 del4/del4 mouse model provides evidence that reduced functional levels of fibrocystin are sufficient for cystogenesis and fibrosis in the liver and pancreas, but not the kidney, and supports the hypothesis of species-dependent differences in susceptibility of tissues to Pkhd1 mutations. (Am J

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Section: Discussionmentioning

confidence: 99%

Biliary and Pancreatic Dysgenesis in Mice Harboring a Mutation in Pkhd1

Gallagher

Esquivel

Briere

et al. 2008

The American Journal of Pathology

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“…Splenic pulp pressure, an indirect measurement of portal pressure (PP) was measured by inserting a fluid-filled 20-gauge needle into the splenic parenchyma [15]. The needle was joined to a PE-50 tube, then connected to a pressure recorder (PowerLab 200 ML 201) and transducer (Sensonor SN-844) with a Chart V 4.0 computer program (ADI Instruments) and finally was calibrated before each experiment.…”

Section: Portal Vein Pressure Measurementmentioning

confidence: 99%

Microsurgical Extrahepatic Cholestasis in the Rat: A Histopathological Liver Study

Aller

Ortega²,

Sánchez-Patán³

et al. 2008

TOPATJ

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Fibrosis, bile duct proliferation and mast cell hyperplasia characterize extrahepatic cholestasis. We studied these liver alterations in a new microsurgical model of extrahepatic cholestasis in the rat. Male Wistar rats: Sham-operated (n=9) and Microsurgical Cholestasis (n=10). After 4 weeks, a liver morphometric study was carried out using an image analysis system to assess bile proliferation and the fibrosis. The liver expression of alpha-smooth muscle actin was assayed by an immunohistochemical technique and mast cells were also counted. Cholestatic-rats presented portal hypertension, portosystemic circulation, and increased (p=0.0001) plasma bilirubin, alkaline phosphatase, Aspartateaminotransferase, Alanine-aminotransferase, and Lactate-dehydrogenase. Plasma levels of Albumin decreased (p=0.001). Cholestatic-rats showed intense biliary duct proliferation (p=0.0001) and fibrosis (p=0.0001). Mast cells accumulate (p=0.0001) around proliferating bile ducts and fibrous septa. The microsurgical cholestasis in the rat induces fibrosis and hyperplasia of bile ducts and mast cells. Mast cell liver infiltration could be an etiopathogenic remodeling factor in experimental cholestasis.

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“…In humans, portal hypertension is characterized by prolonged elevation of portal venous pressure greater than 10 mmHg [2] which leads to hyper-dynamic circulation [3] and the creation of a portosystemic collateral circulation [4], due not only to the opening of preexisting vessels, but also to the formation of new vessels.…”

Section: Introductionmentioning

confidence: 99%