Research On The Correlation Of Ulinastatin With P38MAPK Pathway In The Treatment Of Septic Acute Liver Injury

Objective:To investigate the therapeutic effect of Ulinastatin for Injection(UTI)on acute hepatic injury induced by lipopolysaccharide(LPS)in rats with sepsis,analyzing its related mechanisms and compare with therapeutic effect of inflammatory channel blockers.Methods:Thirty-two healthy male specific-pathogen free SD rats were randomly divided into four groups: blank control group,LPS group,LPS+UTL group and LPS+ channel blocker group.The rats were sacrificed after 24 hours when the model was established,and than took down the levels of alanine transaminase(ALT),bilirubin(BIL)and alkaline phosphatase(AKP)from the blood of rats.Using the method of ELISA tested the level of TNF-? in the liver tissue of rats,the expression of phosphorylated P38 protein in liver tissue was determined by Western-blot and the expression of phosphorylated p38 protein in hepatic tissue was observed by pathology and electron microscope.Results:Compared with the blank group(pathological sections of hepatocytes),there was a significant hepatocyte swelling,hepatocyte degeneration,blurred cell gap,inflammatory cell infiltration and hepatocyte regeneration in LPS group.LPS + UTI group Swelling,water degeneration,inflammatory cell infiltration and liver cell regeneration were lighter than LPS group,but more severe than the blank group.Compared with the blank group(liver tissue electron microscopy),the liver cells ofthe LPS group reflected nuclear pyknosis,cytoplasmic loosening,vacuolar degeneration or steatosis.And the mitochondrial volume significantly increased,the outer membrane boundary became unclear,the mitochondrial ridge was swollen,broken or even disappeared and the structure was unclear.In the LPS + UTI group,it had no obvious hepatocellular pyknosis,mitochondrial volume enlarged slightly,the clear outer membrane boundary,endoplasmic reticulum and mitochondrial ridge(partly broken).LPS + SB group showed nuclear pyknosis,mitochondria slightly swollen and the clear boundary of mitochondrial outer membrane.But the mitochondrial ridge was blurred or broken,endoplasmic reticulum profile was not clear.Compared with the other group,the level of TNF-? and phosphorylated p38 protein in LPS group were significantly higher than other groups(P <0.05)which difference had the meaning of the statistics.There was no significant difference in the level of TNF-? and phosphorylated p38 protein between the blank group,LPS + UTI group and LPS + SB group(P> 0.05).Compared with the blank group,serum ALT was significantly risen in LPS group(P <0.001).LPS+UTI group was lower than LPS group(P < 0.05)but higher than the blank group and LPS + SB group(P <0.001).The blank group and LPS + SB group had no significant distinction(P <0.001).Also,there is no big difference in serum AKP level between the four groups(P> 0.05).The serum BIL of LPS group was significantly higher than the black group(P <0.05).The serum BIL had no significant difference in the black group and LPS+UTI,LPS group and LPS + SB group(P> 0.05).