Effect and Mechanism of Cyclopamine in Reduction of Portal Venous Pressure in Rats with Liver Cirrhosis

Objective To explore the effect of cyclopamine(Cyc) which is the inhibitor of the Hedgehog signaling pathway on portal venous pressure of normal and liver cirrhosis rats,and it's possible mechanisms.Moreover,to provide the experimental basis of drug efficacy and clinical treatment.Methods Thirty two healthy male SD rats were randomly average divided into four groups:normal control group,normal treatment group,liver cirrhosis control group,and liver cirrhosis treatment group.The liver cirrhosis models of rat were established by using the thioacetamide(TAA) method,which made 0.03% of TAA as the initial water concentration,and then the concentration of TAA in drinking water was adjusted according to the changes of the weekly body weight of rats lasting for twelve weeks.In thirteenth week,intraperitoneal injection of corn oil(0.1 ml/100 g body weight,1 time/d) were performed lasting for a week in rats of the normal control group and liver cirrhosis control group;intraperitoneal injection of Cyc(1 mg(0.1 ml)/100 g body weight,1 time/d)were performed lasting for a week in rats of the normal treatment group and liver cirrhosis treatment group.In fourteenth week,the liver function,portal venous pressure(PVP),and the ration of liver or spleen weight to body weight were detected,the expressions of α-smooth muscle actin(α-SMA) and typeⅠcollagen α1(Col1α1) of hepatic stellate cell were detected by using immunohistochemistry.Results PVP were(10.7±0.9) and(12.3±1.3) cm H2O(1 cm H2O=0.098 kPa) in normal control group and normal treatment group,respectivly,the latter was higher than the former(t = -2.918,P = 0.011).PVP were(21.8±0.7) and(14.3±1.4) cm H2O in liver cirrhosis control group and liver cirrhosis treatment group,respectivly,the latter was lower than the former(t = 13.602,P = 0.000).The expressions of α-SMA and Col1α1 in liver cirrhosis treatment group was lower than the liver cirrhosis control group.There were no significant difference of the liver function and ration of liver or spleen weight to body weight between the treatment group and the control group(P0.05).Conclusion Cyclopamine could signally reduce the PVP of liver cirrhosis rats through reducing the expressions of α-SMA and Col1α1.