Rapamycin inhibits compensatory bile duct growth after ischemic injury / 第二军医大学学报

ABSTRACT

Objective: To explore the impact of rapamycin on compensatory bile duct growth in response to ischemic injury. Methods: Male SD rats were randomly assigned to 4 groups sham (n = 28), sham + rapamycin (rapa, n = 28), ischemia (n = 32), ischemia + rapa group (n = 32). Complete hepatic arterial deprivation was performed in the latter 2 groups gastric lavage with rapamycin (2 mg/kg/day) was given to rats in rapa groups. Fresh liver tissues were obtained on day 1, 3, 7, and 14 postoperatively and were subjected to immunohistochemical staining (H-E, Ki-67). Interlobular bile duct within portal tract and periportal bile ductuli were counted in H-E stained sections. Ki-67 positive and negative bile duct epithelial cells were counted in Ki-67 immunolabelled sections. Average intertobular ducts, periportal duculi and ratio of Ki-67 positive epithelial cells/negative epithelial cells were calculated. Results: Ischemia group had obviously increased number of interlobular ducts compared to sham group. Rapamycin lavage inhibited interlobular duct increase on day 7 and day 14 postoperatively compared with ischemia group. In ischemia group Ki-67 (+)/(-) ratio reached its peak level (1.59 ± 0.17) 3 days after operation, being significantly higher than that of sham group. Rapamycin decrease the peak value of Ki-6 7(+)/ (-)ratio. Conclusion: Rapamycin can reduce expression of Ki-67 antigen and inhibit compensatory bil duct proliferation in response to ischemic injury.