Effect of angiotensin-converting enzyme inhibition on experimental hepatic fibrogenesis.
The renin-angiotensin system is suggested to be important in liver fibrogenesis. It induces hepatic stellate cell proliferation and up-regulates transforming growth factor beta-1 (TGF-beta1) expression. Matrix metalloproteinase-2 (MMP-2) is involved in extracellular matrix remodelling. Fibrosis, a consequence of most chronic liver diseases, may be the result of a disturbed balance between fibrogenesis and fibrolysis. The aim of this study was to investigate the effect of enalapril on liver fibrogenesis induced in rats by bile-duct ligation. Forty-seven rats were divided into two groups: bile-duct ligated (BDL) (n = 24) and BDL + enalapril (n = 23). Fibrosis was evaluated by the Knodell scoring system, and TGF-beta1 and MMP-2 were assessed with immunohistochemistry at the second, fourth and sixth weeks after bile-duct ligation. In the BDL group, TGF-beta1 increased by the second week and this increase continued through weeks 4 and 6. In the BDL + enalapril group, TGF-beta1 was significantly lower than the other group (P < 0.05). MMP-2 progressively decreased after week 2 in the BDL group. In the BDL + enalapril group, MMP-2 was significantly higher than the BDL group at the fourth and sixth weeks. These results suggest that enalapril reduces the liver tissue TGF-beta1 and has an ameliorating effect on the fibrosis markers TGF-beta1 and MMP-2.
Türkay
Cansel
C
Department of Gastroenterology, Faculty of Medicine, Fatih University, Ankara, Turkey.
Yönem
Ozlem
O
Arici
Sema
S
Koyuncu
Ayhan
A
Kanbay
Mehmet
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004656:Enalapril / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D053773:Transforming Growth Factor beta1; D004656:Enalapril; D020778:Matrix Metalloproteinase 2