| Objective: To study the influence of radiation on autophagy of hepatic cells,the protective effects of enhanced autophagy for the radiation caused hepaic injury and potential mechanisms.Mehtods:Autophagy in liver tissues was examined by GFP-LC3 staining and Western blot.Radiation caused hepatic injury was evaluated by ALT and AST in serum,H&E,γ H2 AX,and TUNEL staining.L02 cells were used for in vitro study.Chloroquine and rapamycin were used to manipulate the level of autophagy.Results:Total body irradiation(TBI)of 8Gy caused an increase of autophagy in liver tissues and AST levels in serum(P<0.05)at 12 h.Radiation significantly increased the apoptotic and γ H2 AX level in liver tissues.Inhibition of autophagy by chloroquine caused a further increase of AST(IR:345.42±35.25U/L vs IR+CQ:433.42±40.07U/L,P<0.05)and ALT(IR:35.67±8.08U/L vs IR+CQ:98.5 ± 26.67U/L,P<0.05)in serum,and promoted apoptotic and γ H2 AX level in live tissues.However,rapamycin as an autophagy promoter showed protective effects for radiation caused hepatic injury(AST: IR: 345.42±35.25U/L vs IR+Rap:278.42±20.09U/L,P<0.05).Similar changes of autophagy and apoptosis in L02 cells were also observed in control,chloroquine and rapamycin groups.Inhibition of autophagy by CQ caused a increase of ROS in vitro and in vivo,and further increase ALT and AST levels in serum.pretreated with Rap caused a decrease of ROS in vitro and in vivo,and a decrease of ALT and AST levels in serum.Conclusions:The results showed that autophagy contributed to the survival of hepatic cells after IR induced injury and enhanced autophagy could protect hepatic cells by decreasing excessive ROS,which provide a new potential target for the development of new clinical regimens against radiaiton induced liver injury. |
