[Perindopril attenuates the progression of CCl4-inducing rat hepatic fibrosis].

OBJECTIVES

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.

CONCLUSION

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.