Effects Of Simvastatin On Portal Vein Pressure And Hepatic Fibrosis In Rats With Cirrhosis And Portal Hypertension

Objective:To observe whether Simvastatin can lower portal vein pressure in rats with cirrhosis and portal hypertension, and to evaluate the effect on liver fibrosis.Methods:46 male SD rats with cirrhosis and portal hypertension(PHT) model were induced by carbon tetrachloride compound factors. At the end of 8th w,3 rats were randomly selected for PVP measured and histopathology examination.Cirrhosis and PHT rats model was confirmed to be successfully duplicated. Then thirty-four PHT rats were randomly divided into one model group and one treatment group. The treatment group were given simvastatin(20mg/kg/day, for 28days). After treatment, the portal vein pressure (PVP), the mean arterial pressure (MAP), and heart rate (HR) were measured. Serum levels of ALT, AST, TBIL, Alb, HA, LN were detected; pathologic examinations of liver sections were performed by routine HE and Masson staining, and grade of hepatic fibrosis were evaluated according to SSS system.RESULTS:â‘ In a period of 8 weeks, rats with cirrhosis and PHT can be successfully induced by carbon tetrachloride compound factors. The mortality rate of rat's model of PHT is 26.1%.â‘¡Compared with normal rats, PVP of the model group and the simvastatin group were significantly increased (P<0.05), but no change was observed in MAP (P>0.05).â‘¢Compared with normal rats, ALT levels in the model group and the simvastatin group were significantly increased (P<0.05), while Alb levels significantly decreased (P< 0.05), but the difference between the two groups was not significant (P>0.05). No significant changes in AST, TBIL among all the above three groups were observed (P> 0.05).â‘£Compared with normal rats, HA and LN in the model group and the simvastatin group were significantly increased (P<0.05), but the difference between the two groups was not significant (P>0.05). â‘ Compared with normal rats, pathological examination of the model group and the simvastatin group revealed plenty of pseudolobules containing fibrous septa and regeneration nodules of liver cells. As the scores of hepatic fibrosis were significantly increased (P<0.05), but the difference between the two groups was not significant (P >0.05).CONCLUTION:â‘ Cirrhosis and PHT rat model can be successfully induced by carbon tetrachloride compound factors in a relatively shorter time.â‘¡28 days of simvastatin (20mg/kg/d) administration reduces PVP in PHT rats, probably without the improvements in liver function and fibrosis. This suggests that the mechanism of lowering PVP by simvastatin may not involve the change in the hepatic fibrosis level.