器官移植2025，Vol.16Issue(2)：246-255,10.DOI:10.12464/j.issn.1674-7445.2024256
过氧化物酶体增殖物激活受体γ共激活因子-1α在瑞芬太尼抗肝脏缺血-再灌注损伤中的作用研究
Study on the role of peroxisome proliferator-activated receptor γ coactivator-1α in remifentanil against hepatic ischemia-reperfusion injury
摘要
Abstract
Objective To explore the role and mechanism of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)in remifentanil(REM)resistance to hepatic ischemia-reperfusion injury(HIRI).Methods Forty SD rats were randomly divided into sham surgery group,HIRI group,HIRI+REM group,HIRI+PGC-1α inhibitor SR-18292(HIRI+SR-18292)group and HIRI+REM+SR-18292 group,8 rats in each group.HIRI rat models were constructed using non-invasive arterial clip occlusion method,and REM or SR-18292 were intravenously injected before surgery.The liver function indicators and liver tissue adenosine triphosphate(ATP)levels in the serum of rats were detected by assay kits.The activity levels of mitochondrial respiratory chain complexes Ⅲ and Ⅳ(COX-Ⅲ,COX-Ⅳ)in rat liver tissue were assessed by colorimetric methods.The pathological changes in rat liver tissue were observed by hematoxylin-eosin staining.Reactive oxygen species(ROS)and oxidative stress-related indicators in rat liver tissue were measured using the fluorescent probe(DCFH-DA)method and colorimetric methods.The mitochondrial DNA(mtDNA)copies and the expression levels of PGC-1α,nuclear respiratory factor-1(NRF-1)and mitochondrial transcription factor A(TFAM)messenger RNA(mRNA)in rat liver tissue were quantified by real-time fluorescent quantitative polymerase chain reaction(RT-qPCR).And the protein expression levels of PGC-1α,NRF-1 and TFAM in rat liver tissue were assessed by Western blotting.Results Compared with the sham group,rats in the HIRI group showed increased pathological scores and hepatic cell necrosis in liver tissue,elevated levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,and increased levels of ROS and malondialdehyde(MDA)in liver tissue.Additionally,there was a decrease in ATP content and the activity levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),COX-Ⅲand COX-Ⅳin liver tissue,as well as a decrease in mtDNA copies and the expression levels of PGC-1α,NRF-1 and TFAM mRNA and protein(all P<0.05).Compared with the HIRI group,rats in the HIRI+REM group exhibited decreased pathological scores and hepatic cell necrosis,reduced levels of serum ALT and AST,and decreased levels of ROS and MDA in liver tissue.There was also an increase in ATP content and the activity levels of SOD,GSH-Px,COX-Ⅲand COX-Ⅳin liver tissue,as well as an increase in mtDNA copies and the expression levels of PGC-1α,NRF-1 and TFAM mRNA and protein(all P<0.05).In contrast,rats in the HIRI+SR-18292 group showed increased pathological scores and hepatic cell necrosis,elevated levels of serum ALT and AST,and increased levels of ROS and MDA in liver tissue.There was a decrease in ATP content and the activity levels of SOD,GSH-Px,COX-Ⅲand COX-Ⅳin liver tissue,as well as a decrease in mtDNA copies and the expression levels of PGC-1α,NRF-1 and TFAM mRNA and protein(all P<0.05).Compared with the HIRI+REM group,rats in the HIRI+REM+SR-18292 group had increased pathological scores and hepatic cell necrosis,elevated levels of serum ALT and AST,and increased levels of ROS and MDA in liver tissue.There was a decrease in ATP content and the activity levels of SOD,GSH-Px,COX-Ⅲand COX-Ⅳin liver tissue,as well as a decrease in mtDNA copies and the expression levels of PGC-1α,NRF-1 and TFAM mRNA and protein(all P<0.05).Conclusions PGC-1α plays a role in regulating the process of REM resistance to HIRI by promoting mitochondrial biogenesis and reducing the levels of oxidative stress.关键词
肝脏缺血-再灌注损伤/瑞芬太尼/过氧化物酶体增殖物激活受体γ共激活因子-1α/线粒体呼吸链复合物/活性氧簇/线粒体DNA/线粒体转录因子A/核呼吸因子-1分类
医药卫生引用本文复制引用
陈玲利,李秀芳,郝泉水,张喜华..过氧化物酶体增殖物激活受体γ共激活因子-1α在瑞芬太尼抗肝脏缺血-再灌注损伤中的作用研究[J].器官移植,2025,16(2):246-255,10.基金项目
湖北省卫生健康委科研项目(WJ2021M084、WJ2023M176) （WJ2021M084、WJ2023M176）
湖南省人民医院医联体专项科研基金项目(2022YLT006) （2022YLT006）
