Comparison of hepatic fibrosis models and associated hepatic fibronectin expression in Wistar rats treated by bile duct ligation and CCl4

Objective To compare serum biochemical parameters,liver pathology,and fibronectin( FN) expression in Wister rats with hepatic fibrosis induced by bile duct ligation( BDL) and carbon tetrachloride( CCl4). Methods Ninety healthy male Wister rats were assigned to CCl4model( n = 44),CCl4control( n = 6),BDL model( n = 30),and BDL control groups( n = 10). Animal models of hepatic fibrosis were established by intraperitoneal injection of olive oil solution containing 50% CCl4 in the CCl4 model group and by BDL in the BDL group. General conditions of rats were examined. Expression of serum alanine aminotransferase( ALT),serum aspartate aminotransferase( AST),total bilirubin( TBil),and direct bilirubin( DBil) was measured by biochemical analysis. Expression of serum hyaluronic acid( HA) and laminin( LN) was measured by ELISA assay. Pathological changes in liver tissue were examined through hematoxylin- eosin and Masson staining. Expression of FN was assayed by immunohistochemistry. Comparison between groups was made by t test. Results Serum biochemical analysis showed that TBil and DBil levels in BDL model rats increased to and maintained at relatively high levels from day7 after surgery( P < 0. 05); these two parameters in CCl4 model rats increased gradually from week 2 and peaked at week 8 after injection( P < 0. 05). The indicators of hepatic fibrosis,i. e.,HA and LN levels,were significantly higher in the BDL model group than in the CCl4 model group. Pathologically,the CCl4 model group showed diffuse fatty degeneration of liver cells,with extremely significant fiber interval formation in the portal area- portal area or the portal area- central vein; the BDL model group showed coexistence of significant intrahepatic bile duct hyperplasia,inflammatory cell infiltration,and fiber interval formation. In the BDL model group,FN expression was dispersive and irregular with thin fibrous tissues; in the CCl4 model group,FN was mostly expressed in the interlobular septa,with thick fibrous tissues.Conclusion Both BDL and CCl4 can induce hepatic fibrosis in rats. The former induces early increases in the indicators of liver function and hepatic fibrosis and results in significant bile duct hyperplasia,whereas the latter mainly causes fatty degeneration. FN expression shows different distribution patterns in the two hepatic fibrosis models induced by BDL and CCl4.