The Expression Of P38MAPK Signaling Pathway In Liver Failure And Its Significance

Objective:To investigate the expression of p38MAPK signaling pathway in acute-on-chronic liver failure and the relationship with the prognosis of patients with ACLF.Through establishing animal model to explore the effect of p38MAPK in inflammation reaction of liver failure and provide ideas for clinical treatment.Methods:1.Selected 36 patients with acute liver failure in the first hospital affiliated to soochow university infection department during June 2016 to March 2017 as experimental group,and 10 healthy cases as control group in the same period.Using RT-PCR detection to detect the expression of PBMCs of the two groups p38MAPK mRNA expression,Comparing the differences of the two groups expression,as well as ACLF death and survival expression differences.2.Liver failure mice model was induced by CCl₄ joint D-GalN and LPS intraperitoneally.Thirty-two Balb/c mice were randomly divided into normal control group,chronic liver damage group,hepatic failure group,1mg/Kg methylprednisolone therapy group.In addition to the normal group,the rest three sets were injected with 20%CCl₄olive dilution intraperitoneally of 5ml/Kg.Two times per week for 8 weeks.Then the group of 3?4 were injected with D-GalN 500mg/Kg and LPS 100ug/Kg intraperitoneally after 8 weeks.Then the model of ACLF is established.At the same time,the group of 4was treated with 1mg/Kg methylprednisolone for 5 days.3.All mice were sacrificed,observing the pathological changes of liver tissue structure after liver HE staining.Using Western blot and immunohistochemical method to detect the expression and localization of p38MAPK signaling pathway,analysis the relationship between p38MAPK signal transduction and the change of liver failure.Results:1.The expression of p38MAPK mRNA in control group is lower than that of the patients of ACLF,the difference was statistically significant?P<0.05?.The expression of p38MAPK mRNA in the survives of ACLF is lower than that non-survives?P<0.05?.2.HE staining:after 8 weeks,there is no death in the 8 rats of group 1,the shape of liver is normal,the surface of liver is smooth and ruddy color.Then observed under microscope:The hepatic lobule structure integrity,and no liver cell degeneration necrosis.There is 1 death in group 2,the surface of the liver is rough and dark red,hepatocyte fatty change and fibrosis can be observed.Hepatic cells degeneration and necrosis,hyperplasia of fibrous connective tissue,and the formation of false lobular and infiltration of inflammation cells.There is 3 deaths in group 3,liver tissue is hyperemia swelling,the liver cells changed to large or sub-massive necrosis on the basis of fibrosis.Around the portal area,there was inflammatory cell infiltration and accompanied by Hepatic sinus congestion.The liver injury alleviate in group 4 after hormone therapy.3.Immunohistochemical staining result:p-p38MAPK was expressed by sinus cell in early stage,and then by the hepatocyte damage was further continued.the expression level of p-p38MAPK is positively correlated with the degree of liver damage.The expression of p-p38MAPK was significantly higher in liver failure group compared with controls.The positive cells of p-p38MAPK in group of liver failure is the maximum,group2>group1.4.Western blot:The expression of p-p38MAPK increased in liver homogenate of liver failure group,then after hormone treatment,the expression of phosphorylated p38MAPK decreased.The trend of the expression is consistent with immunohistochemical staining in the 4 groups.Conclusion:1.The expression levels of p38MAPK mRNA of ACLF patients were higher than healthy people,which imply that p38MAPK signaling pathway may be the bases of inflammatory of liver failure and plays an important role in the process of liver failure.2.From the result of HE staining,CCl₄ can induce chronic liver damage in mice,combine with D-GalN and LPS can induce acute-on-chronic liver failure,while hormone therapy can improve the degree of liver damage.3.The p38MAPK signaling pathways are activated in the process of liver failure,and participate in inflammation reaction.The signal transduction may also be a new target for novel anti-inflammatory treatment.The hormone treatment can inhibit the pathway activation to play the role of anti-inflammatory.