Objective      To investigate the injury and repair mechanism of mitochondrial DNA damage in rats after hepatic ischemia and reperfusion injury and to determine the intervention effect of rapamycin in the process.       Methods       Whole hepatic ischemia and reperfusion was performed in the rats according to the following ischemia period. The experimental rats were divided into 4 groups

group A (ischemia 30 min)

group B (ischemia 50 min)

group C [intra-gastric injection of 1.5 mg/(kg·d) rapamycin for 3 d before surgery

then ischemia 50 min and rapamycin injection again]

and group D (sham operation). The rats were sacrificed in 24 h

and 3 and 5 d respectively after reperfusion in each group

and their serum levels of AST and ALT were tested and hepatic pathology was observed after HE staining. The mtDNA D-loop region was them amplified and sequenced to find the mutations. The mRNA expression of the mitochondrial DNA  polymerase γ was detected in hepatic tissues by RT-PCR.       Results        In the early stage after injury (24 h)

both serum levels of AST and ALT were increased in groups A

B and C

pathological injury was serious in hepatic tissues

mitochondrial DNA  polymerase γ mRNA expression was increased. Among the 3 injured groups

the indexes were significantly lower in group C than group B (P0.01). After 24 h

the serum levels of AST and ALT were decreased in the 3 groups

the expression level of mitochondrial DNA polymerase γ was gradually decreased in them

with those in the group C more lower (P0.01)

and maintaining at the same level after operation. The mutant rate of mtDNA D-loop region was significantly lower in group C than group B (P0.01).       Conclusion       There are DNA mutations of mtDNA D-loop region in hepatic ischemia-reperfusion injury. Rapamycin attenuates the pathological damage induced by ischemia-reperfusion in rat liver

reduces the mtDNA mutation rate

suppresses the increased expression of mitochondrial DNA polymerase γ

and thus exerts a protective effect against oxidative damage.