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[摘要]：The aim of this study was to investigate if armepavine (Arm, C19H23O3N) could exert inhibitory effects against hepatic fibrosis in rats. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumour necrosis factor-a (TNF-a) to evaluate the inhibitory effects of Arm. Rats were injected with thioacetamide (TAA; 300?mg/kg, intraperitoneally) thrice a week for 4?weeks to induce hepatic fibrosis, with Arm (3 or 10?mg/kg) given by gavage twice a day. Liver sections were taken for western blotting, fibrosis scoring and immunofluorescence staining. Arm (110?mu m) concentration-dependently attenuated TNF-a-stimulated: (i) protein expressions of a-smooth muscle actin (a-SMA), collagen type I and angiopoietin-1; (ii) H2O2 production; and (iii) NF-?B, JunD and C/EBP beta (cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding protein-beta (EBP beta nuclear translocations in HSC-T6 cells. In vivo Arm treatment significantly reduced plasma aspartate transaminase and alanine transaminase levels, hepatic a-SMA expression and collagen contents, and fibrosis scores of TAA-injected rats. Moreover, Arm treatment decreased a-SMA- and NF-?B-positive cells in immunohistochemical staining, and mRNA expression levels of IL-6, TGF-beta 1, TIMP-1, col1a2, iNOS and ICAM-1 genes, but up-regulated the metallothionein gene in the livers of TAA-injected rats. Our results indicated that Arm exerted both in vitro and in vivo antifibrotic effects in rats, with inhibition of NF-?B, JunD and C/EBP beta pathways. Copyright (c) 2011 John Wiley & Sons, Ltd. |
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