Mechanism Research On Macrophage Polarization And Ceramide Metabolism Cause Inflammatory Reactions And Liver Regeneration After Hepatectomy

Background and aimsThe postoperative liver dysfunction(PLD)is still the important postoperative complication after liver resection,which could cause post-hepatectomy liver failure(PHFL).The pathophysiological mechanisms for development of PLD is not yet fully elucidated.Researchs found that hyperactive innate immune response after hepatectomy is the major factor induces PLD even liver failure.Literature shows that excessive inflammatory response can inhibit liver regeneration,while moderate inflammatory response can promote liver regeneration.Macrophages are essential cells constituting innate immune system and play a key role in the process of inflammation.According to their functions and phenotypes,macrophages can be subdivided into two types of polarization:classically activated macrophage(M1)and alternatively activated macrophage(M2).The current study suggests that M1 can promote the development of inflammation by secreting a variety of proinflammatory cytokines,and M2 has anti-inflammatory effects by secreting a variety of anti-inflammatory factors.Emerging evidence demonstrates the role of ceramides(CERs)in hepatocellular death,which contributes to the progression of several liver diseases.Hence,study of ceramide metabolites may help us to understand the mechanism of PLD and find a novel therapeutic avenue to liver diseases.In our study,we perform several experiments to explore the mechanism on macrophage polarization causes inflammatory reactions and liver regeneration after hepatectomy.This will help us to further study the pathophysiology of PLD and provide a new guideline for accurate treatment of PLD.Methods1.Establish M1/M2-polarized macrophages model.2.Establish M1/M2-polarized macrophages intrahepatic transplantation mold in mouse after hepatectomy.3.Study the regulation of macrophage polarization on the inflammatory response and liver regeneration after hepatectomy.4.Set up a protocol to analysis the CERs qualitatively and quantitatively and investigate the correlation between sphingolipid metabolism and macrophage polarization as well as that between sphingolipid metabolism and liver regeneration.Results1.M1/M2-polarized macrophages mold is established.2.M1/M2-polarized macrophages intrahepatic transplantation mold in mouse after liver resection is established.3.M2 macrophages can reduce the liver inflammation and promote liver regeneration be changing the intrahepatic macrophages polarization,while the M1 is the opposite.4.The protocol to analysis CERs qualitatively and quantitatively is set up and we have found preliminarily that there is correlation between sphingolipid metabolism and macrophage polarization as well as that between sphingolipid metabolism and liver regeneration.ConclusionsThrough this study,we find that different phenotypes of macrophages play a significant role in regulating the development of liver inflammatory microenvironment and the process of liver regeneration after liver resection in mice.Our results suggest with cell therapy technology M1/M2 polarized macrophages can affect the liver inflammatory response and the development of liver regeneration after liver resection.The M2 macrophages can significantly inhibit the liver tissue inflammatory response after liver resection,and promote the process of liver regeneration,while the M1 macrophages has the opposite effect.There is correlation between sphingolipid metabolism and macrophage polarization as well as that between sphingolipid metabolism and liver regeneration.Moreover,the successful establishment of the method to analysis CERs qualitatively and quantitatively provides an experimental basis for the study of sphingolipid metabolism in the liver.These results provide experimental basis for further studying the pathogenesis and prevention of PLD even PHFL.