Objective    To explore the preventive effects of simvastatin on ischemic-type biliary lesion (ITBL) after liver transplantation.     Methods    Totally 90 female SD rats

6 to 8 weeks old

weighing 200 to 250 g

were randomly divided into 3 groups

sham-operation group (n=10)

control group (n=40

including 20 donors and 20 receipts)

and experimental group (n=40

including 20 donors and 20 receipts). Rat liver transplantation was established by reconstructing hepatic artery. The rats of experimental group were fed with a normal chow containing 0.1% simvastatin for 1 week before operation and for 2 weeks after operation. The donor liver was stored in the University of Wisconsin solution at 4 ℃ for 12 h followed by transplantation. The animals were killed in 2 weeks after operation and the bile

bile duct and liver tissue were taken. High performance liquid chromatography (HPLC) was used to detect the concentrations of bile salts. Biochemistry

histopathology

immunohistochemistry and RT-PCR were employed to measure the level of phospholipids C

observe the pathological changes of liver

detect the protein and mRNA expressions of phospholipid transfer protein (Mdr2 P-glycoprotein).     Results    The biliary phospholipid composition of rats in the experimental group (3.874 8±1.414 8 mg/dl) was significantly increased

compared with the sham-operation group (1.982 1±0.413 5 mg/dl) and the control group (1.428 5±0.538 7 mg/dl) (P0.05); HE staining showed that the liver bile duct in the control group was severely damaged

while pathological changes in the experimental group were lighter than that of the control group. Bile duct injury severity score ( BDISS) showed the score was (8±1) in the control group and (4±2) in the experimental group

  significantly higher than that in the sham-operation group (0

P0.05).  The expression of Mdr2 mRNA in experimental group was increased more significantly than that of the control group (P0.05).     Conclusion    Simvastatin can effectively increase the phospholipid level in bile of rats after transplantation

which attenuates the pathological changes of liver tissue and effectively protects the transplanted bile duct and liver.