Background and Aims:Hepatic ischemic reperfusion in-jury(IRI)occurring during surgery seriously affects patient prognosis.The specific mechanism of IRI has not been fully elucidated.The study aim was to explore the ch...Background and Aims:Hepatic ischemic reperfusion in-jury(IRI)occurring during surgery seriously affects patient prognosis.The specific mechanism of IRI has not been fully elucidated.The study aim was to explore the changes of in-flammatory environment,and the relationship of the Th17/Treg cell ratio and FOXO1 expression in hepatic IRI.Methods:Liver samples at different ischemic times were collected from patients and mice.The expression of inflammatory markers and FOXO1 in the liver was detected by western blotting and qPCR.Phenotypic changes of liver lymphocytes were analyzed by flow cytometry.The AKT/Stat3/FOXO1 pathway was veri-fied by targeting AKT with GSK2141795.The role of FOXO1 in liver inflammation and changes in lymphocyte phenotype was confirmed by upregulating FOXO1 with resveratrol.Re-sults:Prolonged ischemic time aggravates liver injury in both humans and mouse models of hepatic IRI.IR-stress caused Th17/Treg imbalance and FOXO1 down-regulation by activat-ing the AKT/Stat3/FOXO1 signaling pathway.Upregulation of FOXO1 reversed the Th17/Treg cytokine imbalance and altered the inflammation environment in the liver.Conclusions:Liver IRI induced Th17/Treg imbalance.Upregulation of FOXO1 re-versed the imbalance and alleviated liver inflammation.展开更多
基金the National Natural Science Foun-dation of China(82100664)the Natural Science Foundation of Jiangsu Province(BK20190114+5 种基金Jiangsu Province Postdoc-toral Research Funding Program(2021K116B)Key Project supported by Medical Science and technology development Foundation,Nanjing Department of Health(YKK19070)the Fundamental Research Funds for the Central Universi-ties(0214-YG1312037)Project of Modern Hospital Manage-ment and Development Institute,Nanjing University and Aid project of Nanjing Drum Tower Hospital Health,Education&Research Foundation(NDYG2020047)fundings for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2021-LCYJ-PY-46)the Chen Xiao-ping Foundation for the Development of Science and Technology IRIof Hubei Province,China(CXPJJH121001-2021073).
文摘Background and Aims:Hepatic ischemic reperfusion in-jury(IRI)occurring during surgery seriously affects patient prognosis.The specific mechanism of IRI has not been fully elucidated.The study aim was to explore the changes of in-flammatory environment,and the relationship of the Th17/Treg cell ratio and FOXO1 expression in hepatic IRI.Methods:Liver samples at different ischemic times were collected from patients and mice.The expression of inflammatory markers and FOXO1 in the liver was detected by western blotting and qPCR.Phenotypic changes of liver lymphocytes were analyzed by flow cytometry.The AKT/Stat3/FOXO1 pathway was veri-fied by targeting AKT with GSK2141795.The role of FOXO1 in liver inflammation and changes in lymphocyte phenotype was confirmed by upregulating FOXO1 with resveratrol.Re-sults:Prolonged ischemic time aggravates liver injury in both humans and mouse models of hepatic IRI.IR-stress caused Th17/Treg imbalance and FOXO1 down-regulation by activat-ing the AKT/Stat3/FOXO1 signaling pathway.Upregulation of FOXO1 reversed the Th17/Treg cytokine imbalance and altered the inflammation environment in the liver.Conclusions:Liver IRI induced Th17/Treg imbalance.Upregulation of FOXO1 re-versed the imbalance and alleviated liver inflammation.
