The Effect Of Ganfukan On The Expression Of A-raf,ERK2 In Liver Fibrosis Rat

Objective: To observe the effect of traditional Chinese medicine Ganfu- kan on the expression of A-raf,ERK2(extracellular signal-regulated kinase, ERK)of experimental liver fibrosis rat, explore the role of A-raf and ERK signal transduction pathway in the mechanism of liver fibrosis.Methods: Healthy SD rats, weight 180-220g, were randomly divided into seven groups: normal control group(C group),model group (M group),model control group (MC group),low dose treatment group (LT group ),middle dose treatment group (MT group ),high dose treatment group (HT group ) and medicine prevention group(P group) . Liver fibrosis models of rats were made by subcutaneously injecting with 10%CCl4 for 12 weeks. The liver fibrosis rats in LT group,MT group,HT group were treated with Ganfukang according to low dose,middle dose,high dose from the 9th we- ek to the 20th week, the rats in P group were treated with middle dose Ganfukang from the first week. These rats were sacrificed at the end of the 20th week. The levels of serum alanine aminotransferase (ALT),aspartate Aminotransferase (AST),albumin(ALB),total protein (TP)were measured. The pathological changes of hepatic tissues were observed under light microscopy by HE staining and immunohistochemistry staining; hepatic expression of A-raf,(extracellular signal-regulated kinase) ERKmRNA were detected by reverse polymerase chain reaction(RT-PCR).Results:(1)Serum index: Twenty weeks later, the levels of serum ALT,AST,ALB,GLO,A/G is(37.62±8.94IU,50.02±13.68 IU,39.28±2.38g/L,25.16±3.45 g/L,1.59±0.38)in the middle dose treatment group; in the model group, that is(76.53±10.82IU,85.64±10.62IU,28.46±5.42 g/L,32.53±3.94 g/L,0.96±0.29). (2)Pathology of hepatic tissue:In the HE staining, a great quantity fake-leafit was formed in M group,but it was relieved significantly in the MT group. In the immunohis- tochemistry staining, the expression of ERK2 protein have increased evi- dently in M group compared to C group; the expression of ERK2 protein have decreased in MT group compared to M group(P<0.01). (3)Expression of A-raf and ERK2 mRNA: In reverse polymerase chain reaction(RT-PCR), the expression of A-raf,ERK2 mRNA in M group showed higher levels in hepatic tissue than those in C group(P<0.01); the levels decreased signi- ficantly in MT group in comparison with those in M group(P<0.01). And the expression of A-raf,ERK2 mRNA in P group were downregulated than those in M group, but the difference was not significant.Conclusions: (1)ERK signal transduction pathway maybe played an important role in liver fibrosis.(2)Ganfukan was a good treatment for liver fibrosis,its mechanism of action may be related to effect ERK signal tran- sduction pathway.(3)The treatment effect of MT group is better than LT,HT group, it's a reasonable medication dose.