| The adult liver is the largest organ in the human body.It plays an important role in the metabolism of endogenous substances and the metabolism and clearance of exogenous substances.The liver inflammation caused by a virus,drugs,alcohol or abnormal metabolism of chronic liver injury,inflammation is often accompanied by a common pathological change is excessive extracellular matrix synthesis and abnormal deposition,namely liver fibrosis.In contrast,chronic stimulation leads to liver regeneration constantly,which leads to liver parenchyma and vascular structure form(portal vein system and the hepatic venous system)disorder,forming the so-called regenerative nodules of the liver,liver cirrhosis.Chronic liver injury can lead to cirrhosis and even liver failure or liver cancer.Activation of Raf-1/MEK/ERK1,2 signaling pathway in liver injury.Raf kinase inhibitory protein(RKIP)is a negative regulator of Raf-1/MEK/ERK1,signaling pathway,and it can inhibit the activity of NF-kappa B signaling pathway.Our previous studies have shown that the expression of RKIP in liver fibrosis tissue decreased,with the activation of HSC,the expression of RKIP was significantly reduced,RKIP can inhibit the proliferation of HSC cells,but promote their migration.Further studies in this study confirmed that RKIP can also reduce the adhesion of HSC to matrix collagen.Locostatin is an inhibitor of RKIP activity,and it is a kind of yellow ketone derivative without antibacterial activity.Lin X confirmed by Locostatin intervention model of hepatic fibrosis of liver fibrosis after decreasing the expression of RKIP,Didymin can alleviate hepatic fibrosis by up regulating the expression of RKIP.The preliminary study of this group has confirmed that Locostatin can reduce liver injury,but the protective effect of Locostatin on liver inflammation is not clear.Objective: This paper mainly discusses the effect and mechanism of Locostatin on liver inflammation in mice.Methods: 30 mice were randomly divided into normal control group,carbon tetrachloride model group and Locostatin intervention group.The enzyme,aspartate aminotransferase and liver tissue HE staining and MPO content to determine the changes in the degree of liver inflammation by detection of serum glutamate aminotransferase,through changes of hydroxyproline and liver tissue Masson staining of collagen fibers.Enzyme linked immunosorbent assay(ELISA)was used to detect the lipid peroxidation in liver tissues by T-SOD and MDA.Results:1 Locostatin can reduce the inflammatory activity of liver pathological tissue.In the normal control group 5 mice were sacrificed 1 days after the intervention of the 4 visible liver structure of normal periportal integrity,without expanding,liver cells arranged in neat,uniform size,livercable structure clear,hepatic cord with the central vein as the center to the periphery are arranged radially,liver cells without fatty degeneration and inflammation cell infiltration,but there are 1 mouse liver tissue visible focal necrosis.The normal control group in the intervention of 5 mice which were sacrificed 2 days after the 4 visible liver structure was normal,liver cells arranged in neat,uniform size,livercable structure clear,hepatic cord with the central vein as the center to the periphery are arranged radially,fatty degeneration and inflammatory cell infiltration without liver cells,complete the portal area.In the carbon tetrachloride model group,1 days after the intervention,the rats were significantly enlarged,there were a large number of inflammatory cells infiltration,and the inflammation around the interface was obvious,and the necrosis of the 3 bands and P-C bridging necrosis were observed.Fatty degeneration and necrosis of hepatocytes are common.In the model group,the mice were killed 2 days after the intervention,and the inflammation of the portal area was slightly reduced,and there was a large number of inflammatory cells infiltration,and the inflammation around the interface was obvious,even P-C bridge necrosis.Fatty degeneration of liver cells is common,and focal necrosis can be seen.Locostatin group of mice compared with CCl4 model group mice inflammation is relatively limited,the interval around the interface inflammation is not obvious,occasionally P-C bridging necrosis and hepatic lobule structure is relatively clear,fatty degeneration of liver cells is very common,and visible focal necrosis,inflammation of the liver of mice were killed 1 days later than the Locostatin group mice were killed after 2 days reduced.2 Locostatin can reduce the liver fibrosis stage.After Masson staining,the collagen fibers of the liver tissue could be clearly displayed,and the liver parenchyma cells were stained red,and the collagen staining was blue.In the normal control group,5 mice were killed after the intervention for 1 days and the blue collagen fibers were mainly deposited in the vascular wall and the portal area in the 5 mice after the death of 2 days.The liver tissue of mice with collagen deposition in the CCl4 model group mice were sacrificed 1 days after the intervention and after 2 days increased significantly,the portalarea expanded significantly,the formation of fibrous septa and deep into the hepatic lobule,hepatic lobule structure is not complete,liver sinus showed more blue fiber deposition.Locostatin in the intervention group and intervention mice were sacrificed 1 days after the mice were sacrificed 2 days after the periportal fibrous connective tissue hyperplasia,enlargement of fiber deposition is not obvious,compared with the model group,hepatic lobules were slender,compared to the model group is relatively clear,I see blue sinusoidal fiber deposition.3 Detection of serum ALT and AST markers.The content of serum ALT in CCl4 model group after the last administration were killed after 2 days and the ratio of carbon tetrachloride in model group serum ALT content after the last administration were killed after 1 days was significantly decreased(163.53U/L±41.18 U/L vs 214.33U/L±0.85 U/L,P<0.05,n=5).The content of serum ALT in Locostatin intervention group after the last administration were killed after 2 days and compared to Locostatin group in serum ALT content after the last administration were killed after 1 days was significantly decreased(163.53U/L±41.18 U/L vs 214.33U/L±0.85 U/L,P<0.05,n=5).The normal control group,CCl4 model group and Locostatin group of experimental animal each had 5 mice in the last administration,the content of AST in serum after 1 days were 81.78U/L±9.52 U/L,163.93U/L±32.94 U/L,133.47U/L±4.28 U/L.Carbon tetrachloride model mice serum AST levels were higher than normal control group serum AST content increased(P<0.01,n=5),Locostatin intervention group serum AST content than the normal control group serum AST content increased(P<0.05,n=5).The normal control group,CCl4 model group and Locostatin group with 5 mice each experimental animal in after the last administration,the content of AST in serum after 2 days were 65.70U/L±16.71 U/L,119.90U/L±40.20 U/L,100.72U/L±24.23 U/L.Carbon tetrachloride model mice serum AST levels were higher than normal control group serum AST content increased(P<0.01,n=5),Locostatin intervention group serum AST content than the normal control group serum AST content increased(P<0.05,n=5).The content of serum AST in CCl4 model group after the last administration were killed after 2 days and the ratio of carbon tetrachloride in model group serum AST content after the last administration were killed after 1 days was significantly decreased(119.90U/L±40.20 U/L vs 163.93U/L± 32.94 U/L,P<0.05,n=5).4 SOD content in liver tissueThe normal control group,CCl4 model group and Locostatin group in the three group were in after the last drug content of T-SOD in liver tissue of mice were killed after 2 days than in mouse liver tissue T-SOD content after the last administration were killed after 1 days were significantly lower(253.10U/mg±19.87 U/mg vs 276.06U/mg±17.61 U/mg,P<0.05,n=5)(237.36U/mg±28.35 U/mg vs 260.41U/mg±37.70 U/mg,P<0.05,n=5)and(235.25U/mg±13.09 U/mg vs 268.21U/mg±25.92 U/mg,P<0.01,n=5).5 MDA content in liver tissue.The content of MDA in liver tissues in CCl4 model group after the last administration were killed after 2 days and compared to CCl4 model group in liver tissue MDA content after the last administration were killed after 1 days was significantly decreased(5.14 ?mol/g±1.18 ?mol/g vs 6.15 ?mol/g±0.79 ?mol/g,P<0.05,n=5).6 MPO content in liver tissue.The normal control group,CCl4 model group and Locostatin group with 5 mice each experimental animal in after the last administration,the content of MPO in liver tissues after 2 days were 1.34U/g±0.12 U/g,2.00U/g±0.88 U/g,1.27U/g±0.16 U/g.The CCl4 model group and normal control group mice liver MPO content increased significantly(P<0.01,n=5),CCl4 model group mice in the Locostatin after the intervention,the content of MPO in liver tissue decreased significantly(P<0.01,n=5).The content of MPO in liver tissues in CCl4 model group after the last administration were killed after 2 days and compared to CCl4 model group in liver tissue MPO content after the last administration were killed after 1 days was significantly elevated(2.00U/g±0.88 U/g vs 1.64U/g±0.13 U/g,P<0.05,n=5).7 Hydroxyproline content in liver tissueThe normal control group,CCl4 model group and Locostatin group of experimental animal each had 5 mice in the last administration and hydroxyproline content in the liver tissue after 1 days were 202.15?g/g± 7.29?g/g,254.65?g/g±25.52?g/g,231.43?g/g±15.45?g/g.The CCl4 model group and normal control group mice compared to the liver hydroxyproline content increased significantly(P<0.01,n=5),CCl4 model group mice in the Locostatin after the intervention,the content of hydroxyproline in liver tissue decreased significantly(P<0.01,n=5).However,the content of hydroxyproline in liver tissue of the model group was higher than that of the normal control group(P<0.01,n=5)after Locostatin intervention.The normal control group,CCl4 model group and Locostatin group with 5 mice each experimental animal in after the last administration of liver hydroxyproline content after 2 days were 191.98?g/g±5.59?g/g,243.27?g/ g±29.32?g/g,208.56?g/g±19.35?g/g.The CCl4 model group and normal control group mice compared to the liver hydroxyproline content increased significantly(P<0.01,n=5),CCl4 model group mice in the Locostatin after the intervention,the content of hydroxyproline in liver tissue decreased significantly(P<0.01,n=5).Liver hydroxyproline content in group Locostatin after the last administration were killed after 2 days and Locostatin group than in the liver tissue hydroxyproline content after the last administration were killed after 1 days was significantly decreased(208.56?g/g±19.35?g/g vs 231.43?g/g±15.45?g/g,P<0.05,n=5).Conclusion: Locostatin can reduce inflammatory cell infiltration,reduce carbon tetrachloride induced liver tissue inflammation in mice,and then delay the mitigation of carbon tetrachloride induced liver fibrosis in mice. |
PDF Full Text Request