Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

Abstract

Liver cirrhosis clinically shows thrombocytopenia and hypersplenism. Although splenectomy is performed to achieve higher platelet count and better hemostasis, the effect of splenectomy for liver cirrhosis remains unclear. The aim of the present study that was focused on serotonin was to investigate the relationship between splenectomy and liver regeneration in rats with secondary biliary cirrhosis. Liver cirrhosis was induced in Sprague-Dawley rats by bile duct ligation (BDL). In addition, splenectomy and administration of ketanserin, which selectively antagonizes 5-HT2A and 2B serotonin receptors, were performed. Three weeks after the interventions, whole blood, plasma, serum, and liver specimens were obtained for the following studies: peripheral platelet counts, hemodynamics of serotonin, histopathological examination, immunostaining, and quantification of mRNA expression. Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters: hepatocyte ratio to the entire liver area, Ki67-positive hepatocyte count, and expression of phosphorylated extracellular signal-regulated kinases. This enhancement of liver regeneration was negated by ketanserin. Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions.