Effects of imatinib mesylate on rat hepatic fibrogenesis and the expression of transforming growth factor-?1 / 中华消化杂志

ABSTRACT

Objective To investigate the anti-fibrogenesis property of imatinib mesylate in a rat model of liver fibrosis induced by carbon tetrachloride/olive oil and its effect on the expression of trans- forming growth factor(TGF)-?1.Methods Rat liver fibrosis was induced by intraperitoneal administra- tion of carbon tetrachloride and olive oil mixture twice a week for eight weeks.Imatinib mesylate was given 20 mg/kg daily by oral lavage.The control rats received saline by oral iavage.Liver collagen depo- sition was evaluated by immunohistochemistry with Masson staining.The activation of hepatic stellate cells was detemined by the immunohistoehemistry staining of?-smooth muscle actin.The mRNA expres- sions of TGF-?1,c-Abl and TIMP-1 were measured by RT-PCR.While protein expressions of TGF-?1, phosphorylated platelet-derived growth factor receptor and c-Abl were detected by Western blot and im- munohistochemical staining.Hepatic hydroxyproline content was also quantified.Results The collagen deposition[(16.23?1.01)%vs(25.61?0.92)%]and the number of activated HSCs(10.52?1.33vs 13.10?1.21)were reduced in the imatinib mesylate treatment group compared with the control group by 35% and 20%,respectively(P