Microsurgical Extrahepatic Cholestasis in the Rat: A Histopathological Liver Study

Abstract

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.

Mast cell-mediated splanchnic cholestatic inflammation

“…There is evidence that mast cells are involved in various hepatobiliary disorders, such as chronic liver diseases and biliary/cholestatic diseases [34,35]. This suggests that they are at least involved in inflammation and periportal fibrosis [12,[35][36][37]. In addition, mast cells produce cytokines and growth factors that can promote excessive biliary epithelial cells proliferation [29].…”

“…It was suggested that mast cells, involved in both innate and adaptive immunity [10,11], could be correlated with the evolution of experimental portal hypertension [2] and experimental hepatic chronic disease [1,12]. This is the reason why we have studied the hepatic-spleen-intestinal and mesenteric lymph node distribution of mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) in an experimental model of chronic liver insufficiency secondary to microsurgical obstructive cholestasis in the rat [13].…”