Rapamycin Delays Recovery Of Ischemia/Reperfusion-Impaired Liver In Mice

Objective To investigate the effect of Rapamycin on recovery of ischemia/reperfusion liver in mouse.Methods The left-median liver lobe ischemia/reperfusion model was performed in mice. The mice in the experiment were randomly divided into four groups: (1) rapamycin-treated surgery group (group A, n=16): the mice were administered with rapamycin at a primary dose of 3mg/kg/d and maintained dose of 1mg/kg/d, then received the ischemia/reperfusion operation at day 4; (2) normal saline-treated surgery group (group B, n=16): the mice were given normal saline at a dose of 0.2ml/d, then underwent the ischemia/reperfusion operation at day 4; (3) rapamycin-treated sham surgery group (group C, n=12): the mice were administered with rapamycin at a primary dose of 3mg/kg/d and maintained dose of 1mg/kg/d; then underwent the sham-operation at day 4; (4) normal saline-treated sham surgery group (group D, n=12): the mice were given normal saline at a dose of 0.2ml/d, then received the sham-operation at day 4. The mice received the treatments till the experiment was over. A half of the mice in each group were executed at day 1 after surgery and another half at day 4 after surgery. Histological changes were evaluated; Expressions of proliferating cell nuclear antigen(PCNA) and CyclinD1 were detected by immunohistochemistry in the livers.Results At day 1 after surgery, histological changes of the livers in group A were obviously more severe than that in group B; at day 4 after surgery, histological injuries of the livers in group A had not improved significantly, in comparison, the injuries had improved markedly in group B; no histological changes were observed in group C and group D. Expression of PCNA in group A was obviously lower than that in group B at day 1 after surgery (40.1% vs 52.3%, p<0.05)and day 4 after surgery (26.6% vs 35.5%, p<0.05), so was the expression of CyclinD1, as shown by 36.0% vs 38.1% (p< 0.05) at day 1 after surgery and 21.6% vs 29.4% (p<0.05) at day 4 after surgery. No expressions of PCNA and CyclinD1 were found in both group C and group D.Conclusion Rapamycin delays recovery of ischemia/reperfusion liver in mice, which associates with the inhibition of hepatocyte proliferation. Rapamycin do not harm to the normal liver tissue.