Multi-omics Analysis The Mechanism Of Hepatic Ischemia Reperfusion Injury

Hepatic ischemia reperfusion injury is the leading cause of liver dysfunction and failure after liver surgery or transplantation without effectively therapeutic strategies.Therefore,in-depth study of the molecular mechanism of hepatic ischemia reperfusion injury and the search for the key factors and signaling pathways regulating hepatic ischemia reperfusion injury can provide scientific basis for the development of new strategies for the treatment of hepatic ischemia reperfusion injury and provide potential targets for clinical prevention and treatment.In order to systematically explore the regulatory mechanism of hepatic ischemia reperfusion injury,this study analyze transcriptome and proteome data of different stages of hepatic ischemia reperfusion from SRA and ProteomeXchange database to reveal the change of molecular events by various bioinformatics analysis methods.The biological events and signal pathways that significantly change in different stages of hepatic ischemia reperfusion injury are described,and then combined analysis was conducted to find the key factors and signal pathways in hepatic ischemia reperfusion injury.At the transcriptional level,hepatic ischemia reperfusion injury can be divided into six stages: metabolic disorder,Kupffer cell activation,inflammatory explosion,cell death,injury repair,and functional recovery.After further analysis,we find that the inflammatory response and apoptotic response in the 0-6 h stage of reperfusion may be directly related to the degree of liver damage.Therefore,we focus on the inflammatory activation and apoptotic response stage at the early stage of hepatic ischemia reperfusion,and we use Animal TFDB database to screen out 12 transcription factors that are highly expressed at the early stage of ischemia reperfusion,such as Egr1,which may regulate the inflammatory activation at the early stage of ischemia reperfusion.At the same time,we screened out a number of molecules negatively related to inflammation and apoptosis response through correlation analysis,which may have anti-inflammatory and anti-apoptotic effects.The changes in molecular events at protein levels are less pronounced and orderly than at transcription levels,and the relatively obvious inflammatory response did not appear until the 12 h stage of reperfusion.Therefore,at the protein level,we pay more attention to directly looking for functional proteins related to hepatic ischemia reperfusion injury.Through protein interaction analysis,we find that there is a close relationship between Serpina protein family,Apo protein family and inflammation.Meanwhile,through correlation analysis and DisGeNET database,we find that Tollip,Sod2 and other molecules that regulate inflammation and apoptosis are significantly related to the occurrence and development of hepatic ischemia reperfusion injury.These molecules may become markers or effective therapeutic targets of hepatic ischemia reperfusion injury.