Effect of propofol on hepatic cell apoptosis induced by ischemia-reperfusion in rats

Objective To investigate the sinusoidal endothelia) cell (SEC) apoptosis induced by hepatic ischemia-reperfusion (I/R) and the effect of propofol on the hepatic cell apoptosis in vivo. Methods For hepatic I/R study we utilized a rat model of 70% liver ischemia according to Kohli, et al . Twenty-four male SD rats weighing 250-350 g were randomly assigned to 3 equal groups of eight animals : group A was subjected to 30 min of liver ischemia followed by 6 h of reperfusion and normal saline was infused iv at the onset of reperfusion, at a rate 10 ml · kg-1 · h -1 for 60 min; group B was subjected to the same J/ R as in group A but instead of NS propofol 20 mg kg was given iv followed by continuous infusion of 0.5% propofol at 50 mg· kg-1 · h-1 for 60 min; group C underwent sham operation followed by intravenous NS infusion at 10 ml kg h for 60 min. Blood samples and liver biopsies were obtained at the end of 6h of reperfusion, for determination of plasma alanine aminotransferase (ALT) activity and hepatic malondialdehyde (MDA) content, apoptosis and microscopic examination (light and electron microscopy) . Apoptosis was determined both qualitatively and quantitatively by DNA laddering and TUNEL methods. Results In group A there was a significant increase in apoptotic hepatocytes and SEC after I/R as compared with group C ( P 0.01 ) . Most of TUNEL positive cells were SEC and only a small number of hepatocytes underwent necrosis and apoptosis. In group B the number of TUNEL-positive SEC and hepatocytes was significantly smaller than that in group A ( P 0.01 ) and formation of hepatic DNA fragmentation was also greatly reduced. The degree oi hepatic necrosis, plasma ALT activity and liver MDA content decreased significantly in group B as compared with those in group A ( P 0.01 ) . Electron microscopic examination showed that both SEC and hepatocyte injuries were much slighter in group B than those in group A. Conclusion Apoptosis is the key mechanism of hepatic cell death in the early stage of reperfusion.characterized by apoptosis of SEC.Propofol inhibits not only hepatocyte necrosis but also SEC and hepatocyte apoptosis after I/R through its antioxidant effect.