The Animal Experiment Research Of MgIG On Acute Liver Failure By Modulating ERK1/2 Signaling Pathway

Objective To more investigate the anti-inflammatory mechanism of magnesium isoglycyrrhizinate(MgIG)on the rats of acute liver failure(ALF)by observing the effects of MgIG on ALF rats and detecting the ERK1/2 signaling pathway related protein,liver function and prothrombin activity in ALF tissues.Methods The Wistar rats were randomly divided into the following five groups(n=12/group): normal control,ALF model(model),25,50 and 100mg/kg MgIG.And model group,MgIG 25mg/kg treatment group,MgIG 50 mg/kg treatment group and MgIG 100mg/kg treatment group were established ALF rat models by lavageing with CCl4.After 24 hours of established models,they acceped treatment with 0.9% saline and three different doses of MgIG(25mg/kg,50mg/kg and 100mg/kg).The activities,hairs,spirits,weights and the survival time of the rats in each group were observed within 48 hours.Meanwhile,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and prothrombin activity(PTA)in blood were analyzed.When the rats were sacrificed,the liver tissues were removed and their pathological changes were observed.Reverse transcription polymerase chain reaction(qRT-PCR)detectes the expression of ERK1/2 mRNA and Western blotting detectes the protein expression changing of ERK1/2 and p-ERK1/2 in liver tissues.Results1.Observation of rats general state of health: model group rats gradually appear apathetic,rough hair,yellow urine,no resistance to caught,activities decreased,weights decressed,reaction dullness,and even bleeding in nose and mouth,Compared to model group,the situations of MgIG groups have improved,including spirits,behave apathetic,hairs,reaction,urine,weight and shape changes of liver tissues with the increased administration doses.2.The analysis of liver function:2.1 The liver function of the model group is significantly worse,and ALT and AST are significantly increased and the levels of PTA were significantly decreased.The levels of ALT,AST and PTA are significantly improved in MgIG treatment groups with the increased MgIG doses.2.2 Compared with control group,the levels of ALT,AST and PTA in the three MgIG treatment groups(25mg/kg,50mg/kg and 100mg/kg)are significantly improved,and the differences are statistical significance(p <0.01).2.3 Compared with model group,the levels of ALT,AST and PTA in MgIG 25mg/kg group have improved,and the differences are statistical significance(p> 0.05).2.4 Compared with model group,MgIG 50mg/kg group showed lower level of ALT has significant statistical significance(P<0.01),and higher levels of AST and PTA have no statistical significance(p> 0.05).2.5 Compared with model group,the levels of ALT,AST and PTA in MgIG 100mg/kg group have improved,and the differences are statistical significance(p<0.05).2.6 Compared with MgIG 25mg/kg group,the levels of ALT,AST and PTA in MgIG 50mg/kg group are improved,and the differences are statistical significance(P<0.05);compared with MgIG 25mg/kg group,the levels of ALT and AST in MgIG 100mg/kg group have decressed,and the differences have significant statistical significance(p <0.01),and the level of PTA in MgIG 100mg/kg group have increased,but the differences have on statistical significance(p>0.05).2.7 Compared with MgIG 50mg/kg group,the levels of ALT and AST in MgIG 100mg/kg group have decressed,and the differences have statistical significance(p <0.05),and the level of PTA in MgIG 100mg/kg group have increased,but the differences have on statistical significance(p>0.05).3.The ERK1/2 mRNA expression: The ERK1/2 mRNA expression: The expressions of ERK1/2 mRNA significantly increased in experiment group(P <0.01).The expression of ERK1/2 mRNA in the experimenta group was significantly decreased after treatment with MgIG.Compared with ALF model group,MgIG(50mg/kg)and MgIG(100mg/kg)groups showed lower levels of ERK1/2 mRNA(p <0.05),while there is on difference among MgIG treatment groups(p> 0.05).4.The protein expression of ERK1/2 and p-ERK1/2 :4.1 The expression of ERK1/2 protein in liver tissues of control group,model group,MgIG 25mg/kg group,MgIG 50mg/kg group and MgIG 100mg/kg group was not statistically significant(p> 0.05).4.2 The p-ERK1/2 protein was up-regulated in the liver tissues of model group,MgIG 25mg/kg group,MgIG 50mg/kg group and MgIG 100mg/kg group.The expression of p-ERK1/2 protein in model group and MgIG treatment group is significantly higher than that in control group(p<0.01).Compared with MgIG 25mg/kg group,MgIG 100mg/kg group can reduce the expression of p-ERK1/2 protein(p <0.05).Conclusion1 Acute liver failure is closely related to the activation of ERK1/2 signaling pathway;2 The anti-inflammatory and hepatoprotective effects of MgIG may be related to down regulation of ERK1/2 signaling pathway.