〔Abstract〕 To investigate the role and mechanism of PGC-1α-mediated mitochondrial biosynthesis in AMP-activated protein kinase (AMPK) agonist anti-hepatic ischemia-reperfusion injury (HIRI) . Methods SD rats were randomly divided into Control group , HIRI group , HIRI + AICAR group , HIRI + SR-18292 group and HIRI + AICAR + SR-18292 group , with 8 rats in each group . The rats were intraperitoneally injected with AICAR (500 mg/ kg) or SR-18292 (32 mg/kg) before operation , and then the HIRI model was established by non-invasive vascular clamp clamping method . The samples were taken 24 hours after reperfusion . The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and the levels of malondialdehyde (MDA) , superoxide dis- mutase (SOD) and adenosine triphosphate (ATP) in liver tissue were detected . HE staining was used to observe the pathological changes of liver tissue . The level of reactive oxygen species (ROS) and the changes of mitochondri- al membrane potential in liver tissue were detected by fluorescence probe . The copy number of mitochondrial DNA ( mtDNA) and the mitochondrial biosynthesis-related genes PGC-1α, NRF1 , TFAM , UQCRC2 and other mRNA ex- pression levels were detected by qRT-PCR . Western blot was used to detect the protein expression levels of AMPKα,p-AMPKα, mTOR , p-mTOR , PGC-1 α and TFAM in liver tissue . Results Compared with the control group , the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI group increased , while the levels of SOD and ATP decreased ( all P < 0. 05) . At the same time , the mtDNA copy number , mitochondrial membrane potential and the mRNA expression levels of PGC-1 α, NRF1 , TFAM , and UQCRC2 in liver tissues de- creased , and the protein ratio of p-AMPKα/AMPKαand the protein expression levels of PGC-1 α and TFAM de- creased . The ratio of p-mTOR/mTOR protein increased (both P < 0. 05) . Compared with HIRI group , the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI + AICAR group decreased , while the levels of SOD and ATP increased (all P < 0. 05) . At the same time , the mtDNA copy number , mitochondrial membrane potential and the mRNA expression levels of PGC-1 α, NRF1 , TFAM , and UQCRC2 in liver tissue increased , and the protein ratio of p-AMPKα/AMPKαand the protein expression levels of PGC-1 αand TFAM increased . The ratio of p-mTOR/mTOR protein decreased (both P < 0. 05) . However , combined with SR-18292 intervention , the protective effect of AICAR on liver tissue of HIRI rats was significantly reversed . Conclusion PGC-1 αmediated mitochondri- al biosynthesis is involved in the regulation of AMPK agonist-mediated protective effect of HIRI , and its mechanism may be related to the activation of AMPK/mTOR signaling pathway .