[Effects of perindopril and valsartan on the expression of TGF beta 1 and TGF beta receptor II mRNA, Smad3 and Smad7 in experimental hepatic fibrotic rats].
OBJECTIVE
To investigate the therapeutic effects of perindopril, an angiotensin-converting enzyme inhibitor, and valsartan, an angiotensin II receptor blocker on TGFbeta1 and TGFbeta receptor II mRNA, Smad3 and Smad7 on rat liver fibrosis.


METHODS
60 Wistar rats were randomly divided into four groups (each group, n=15). Group 1 rats were not treated and served as healthy controls. The rats of groups 2,3,and 4 were injected with CCl(4) which induced liver fibrosis. After four weeks, group 3 rats started a treatment of perindopril, and group 4 rats with valsartan. All rats were sacrificed at the eighth week and their blood and livers were collected for analysis. The effects of perindopril and valsartan were evaluated by the levels of transforming growth factor-beta1 (TGFb1), and TGF receptor (TGFb1RII) mRNA in liver tissues by RT-PCR, the expressions and sites of TGFb1, Smad3 and Smad7 in liver tissue by immunohistochemical staining. The liver histopathology was also examined with HE staining, and the hydroxyproline in the liver and serum hyaluronic acid (HA) were examined using biochemsitry and RIA.


RESULTS
Compared with the control group, the levels of TGFb1, TGFb1RII mRNA and the expression Smad3 were significantly decreased in the two treated groups, and the expression of Smad7 was also remarkably increased in the livers of rats treated with perindopril or valsartan. The histological changes of fibrosis, the hydroxyproline in the livers and HA were also improved in the treated rats.


CONCLUSIONS
Perindopril and valsartan have a protective effect on liver injury and can inhibit hepatic fibrosis induced by CCl(4) in rats. Their mechanisms may be associated with their effects of down-regulating TGFb1, TGFb1RII mRNA and smad3, and up-regulating Smad7 which then resulted in suppressing the activation of hepatic stellate cells.
Gong
Zuo-Jiong
ZJ
Department of Infectious Diseases, Renmin Hospital, Wuhan University, Wuhan 430060, China.
Song
Shi-Ling
SL
Huang
Yan-Qing
YQ
Ruan
Peng
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D051900:Smad3 Protein / Q000096:biosynthesis* / Q000235:genetics; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D051906:Smad7 Protein; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000068756:Valsartan; D002251:Carbon Tetrachloride; D014633:Valine; D020913:Perindopril