The Role And Mechanism Of Pyroptosis In Hepatic Ischemia-reperfusion Injury

Aims:Ischemia-reperfusion injury（IRI）in liver surgery is an important clinical pathological process.According to different types of clinical operations,there are two forms of liver ischemia-reperfusion injury,warm ischemia reperfusion injury,exists in general liver surgery,and warm ischemia-cold ischemia-reperfusion injury,the main injury in clinical liver transplantation.IRI affects the success of surgery and liver transplantation to a large extent.Inflammatory response plays an important role in the pathological process of liver IRI.Excessive inflammatory response can cause a two-hit to hepatocyte.Pyroptosis,a highly proinflammatory cell death method,is a new type of programmed cell death discovered in recent years,which is characterized by swelling and lysis of cells accompanied by the release of large amounts of cell contents（DAMPs）and inflammatory factors.A large number of studies have shown that pyroptosis plays a key role in various diseases and injury processes,but its role in liver IRI remains unclear.Previous articles suggest that there is a phenomenon of pyrolysis of cells during ischemia-reperfusion injury,which is related to the inflammatory response and the degree of injury.Therefore,studying the role of pyrolysis in liver ischemia-reperfusion and whether blocking cellular pyrolysis can protect liver IRI will provide a valuable experimental basis for the treatment of liver IRI.Methods:In the mouse liver IRI model,the left outer lobe and middle lobe of the liver were blocked by non-damaging vascular clips for 90 min,and then reperfusion for 6 h.Various methods were used to verify the existence of pyroptosis in the liver of mice.Blocking pyroptosis by inhibitors and hepatocyte-specific Gsdmd-knockout(Alb Cre+Gsdmd^f/fand Myeloid-specific Gsdmd-knockout(Lysm Cre+Gsdmd^f/f)mice.HE staining Immunohistochemical staining,ELISA,western blot,PCR and other methods are used to detect the degree of liver tissue damage.Results:The activation of caspase-1 and the pyroptosis occur in the liver IRI of mice.Myeloid-specific Gsdmd-knockout can improve inflammatory infiltration and tissue damage after liver ischemia-reperfusion,but hepatocyte-specific Gsdmd-knockout liver cannot reduce liver ischemia-reperfusion injury.Conclusion:Pyroptosis mainly occurs in immune cells of myeloid origin during liver IRI injury.Blocking the pyroptosis can protect the liver IRI.