Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion.
The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1.
Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.