Effect Of IL-10 On The Expression Of Growth Factors And ECM And Related Metabolizing Enzyme In Experimental Hepatic Fibrosis Rat

Objective To study the effect of IL-10 on the expressionof TGF-β1,EGF,HGF and PDGFof HSC and MMP-2,MMP-9,TIMP-1,Collgen-Iand Collgen-III of liver tissue of hepatic fibrosis rat and theantifibrogenic role of exogenous IL-10.Methods The experiment was separated to two periods.The first stage,60 Spraque-Dawly(SD)rats were randomly divided into three groups:normalcontrol group1(GN1,8 rats),hepatic fibrosis group(GC,28 rats)andIL-10 intervened group(GI,24 rats). At the beginning of the 7th and11th week,HSCs were isolated,RT-PCR and immunocytochemistry wereperformed to detect the expression of growth factors of HSCs. Histologicalexamination was used to determine the degree of hepatic fibrosis. Thesecond stage, 47 SD rats were randomly divided into two groups,normalcontrol group2(GN2,6 rats)and CCl4group(GZ,41 rats). At the end of9th week,rats in GZ were randomly allocated into three groups:model group(GM,9rats),IL-10 treated group(GT,9 rats)and recovered group(GR,9rats).At the end of 12th week,all rats were sacrificed. Immunohistochemistrywere exerted to detect the expression of MMP-2,MMP-9,TIMP-1,Collgen-Iand Collgen-III of liver tissue,Histological examination was used todetermine the degree of hepatic fibrosis.Results The first stage,rat hepatic fibrosis was developed and HSCs wereisolated successfully. At the 7th and 11th week,TGF-β1,EGF,and HGFmRNA in GC increased obviously compared with GN1 and GI. For TGF-β1,no difference was seen between GI and GN1. For EGF,mRNA level in GIincreased compared with GN1. For HGF,mRNA level in GI decreased comparedwith GN1. Between these two time points,TGF-β1 expression at the 7thweek was higher than that of the 11th week;but for EGF,the former islower than the later. As to PDGF mRNA,there was no significant disparityby statistical analysis among/in these groups,but difference seemed toexist in protein. Results by immunocytochemistry of TGF-β1 and EGF wereparalleled with the above findings. The second stage,rat hepatic fibrosiswas developed as showed by histological examination,the degree of hepaticfibrosis in GT alleviated obviously compared to GM,and the change in GRwas not distint. The positive expression of MMP-2,MMP-9,TIMP-1,Collgen-Iand Collgen-III displayed as follows,compared to GN2,they increasedclearly in GM;after treated with IL-10,they declined obviously;theexpression of them in GR decreased,but still higer than GT.Conclusions The expression of TGF-β1,EGF,HGF,MMP-2,MMP-9,TIMP-1,Collgen-I and Collgen-III increased with the progression of hepaticfibrosis and decreased after treatment with IL-10. IL-10 plays anantifibrogenic role by suppressing their expression.