| Background: Acute liver failure is a critically ill disease with a very high mortality rate,and its pathogenesis is still not fully understood.Our recent studies have confirmed that the UII/UT system plays a key role in the development of ALF,and this signaling system activation mediates the immune inflammatory injury response of ALF liver tissue.P120 ctn is an important molecule in the innate immune response of vascular endothelial cells and epithelial cells,and plays an important role in inflammatory injury response,but its role in ALF is unclear,especially in the UII/UT system-mediated intrahepatic immune inflammation of ALF.The role of the reaction needs to be further studied.Objective: To investigate the effect of urantide,a urotensin II receptor antagonist,on hepatic p120-catenin(p120ctn)expression in acute liver failure(ALF)mice.Methods: Six-week-old healthy BALB/c mice were randomly divided into four groups: group A was healthy control group LPS/D-GalN(-)urantide(-),group B was pretreatment control group LPS/D-GalN(-)urantide(+),group C is ALF model group LPS/D-GalN(+)urantide(-),group D is pretreatment ALF group LPS/D-GalN(+)urantide(+)[each Group 6(n=6)].Groups B and D were given pretreatment with urantide in the tail vein,and groups A and C were given an equal volume of saline control in the tail vein.After 30 min,groups C and D were given intraperitoneal injection of LPS/D-GalN to induce acute liver injury.Groups A and B were intraperitoneally injected with the same volume of saline control.Six hours after intraperitoneal injection,the blood of the mice was collected by eyeball blood collection combined with cardiac blood sampling,and mouse liver tissue samples were collected.Paraffin was embedded,sectioned,and the liver pathology of eachgroup of mice was observed.The relative quantitative detection of p120 ctn mRNA in liver tissue was detected by Quantitative Real-time PCR(qRT-PCR).The p120 ctn protein was detected by Western-blot.The expression levels of serum cytokines(TNF-?,IL-6 and IL-10)in each group of mice were detected by antibody sandwich method.Results: At 6 hours after LPS/D-GalN injection,the pathological damage of liver tissue was obvious.Under light microscope,the hepatic lobular structure was destroyed,hepatocyte degeneration and necrosis,inflammatory cell infiltration and hepatic tissue interstitial congestion were pathological changes.After injection of UII receptor antagonist urantide,degeneration and necrosis of hepatocytes were significantly reduced,inflammatory cell infiltration and hepatic interstitial congestion were significantly reduced.In addition,the expression of p120 ctn mRNA and protein in group C was significantly lower than that in group A and B(P<0.01).After using urantide,the expression of p120 ctn mRNA and protein in group D was significantly increased(P<0.01).).At the same time,the expression of pro-inflammatory cytokines(IL-6 and TNF-?)in group C was significantly higher than that in groups A and B.The expression of anti-inflammatory cytokines(IL-10)was significantly lower than that in groups A and B,but after using urantide.The expression of pro-inflammatory cytokines(IL-6 and TNF-?)in group D was significantly lower than that in group C,and the expression of anti-inflammatory cytokines(IL-10)was significantly higher than that in group C.Conclusion: LPS/D-GalN induced significant inflammatory damage in liver tissue of ALF mice,and the release of pro-inflammatory cytokines increased significantly.After urantide,liver tissue inflammation was significantly reduced and proinflammatory cytokine release was down-regulated.In addition,LPS/D-GalN induced down-regulation of p120 ctn gene and protein expression in liver of ALF mice,and up-regulation of p120 ctn gene and protein in liver after urantide pretreatment.The above results indicate that the UII/UT system inhibits the expression of p120 ctn in the liver during mediation of ALF liver injury and proinflammatory cytokine release.Thissuggests that the UII/UT system may mediate the liver damage effects of ALF by inhibiting p120 ctn in the liver. |
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