[Perindopril attenuates the progression of CCl4-inducing rat hepatic fibrosis].
OBJECTIVE
The aim of the present study was to determine the effects of angiotensin-converting enzyme inhibitor, perindopril, on the progression of rat hepatic fibrosis induced by CCl4.


METHODS
Male wistar rats weighting about 250g were treated with perindopril (2mg/kg, daily gavage), except for model group and control group. After 4, 6 weeks, morphological examination was based on microscopy. RT-PCR was utilized to detect gene expression of angiotensin II type 1 receptor (AT1 receptor) in the liver. Meanwhile, the protein expressions of AT1 receptor, transforming growth factor beta 1 (TGF-beta1) and platelet-derived growth factor-BB (PDGF-BB) in liver tissue were examined by Western blot. The activity of matrix metalloproteinase-2 (MMP-2) was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radio-immunity technique.


RESULTS
RT-PCR and Western blot revealed that there was a up-regulation in AT1 receptor expression in model group compared with control group. Perindopril treatment significantly reduced mean fibrosis score, messenger RNA and protein levels of AT1 receptor, protein levels of TGF-beta1 and PDGF-BB, Serum levels of HA and LN, and MMP-2 activity.


CONCLUSIONS
These results suggest that angiotensin II may play an important role in fibrosis of liver. Perindopril may have a inhibiting effect on CCl4-induced hepatic fibrogenesis of rat.
Li
Xu
X
The PLA Institute for Digestive Diseases, Nanfang Hospital, The First Medical University of PLA, Guangzhou 510515, China.
Meng
Ying
Y
Yang
Xi-shan
XS
Zhang
Zhen-shu
ZS
Wu
Ping-sheng
PS
Zou
Jun-ling
JL
D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D000077214:Becaplermin; D002251:Carbon Tetrachloride; D020913:Perindopril