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

2004 
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 40 male wistar rats weighting about 250 g were divided into 3 groups. Model group (Mo): the rats were injected with 40% CCl4 0.25 g/L subcutaneously three times a week. Perindopril group (Pe): the rats were injected with 40% CCl4. Perindopril, equivalent to 2 mg/kg/d, was given ig. Control group (Nc): the rats were injected with olive oil only. After 4,6 weeks, morphological examination was based on microscopy. RT-PCR was utilized to detect gene expression of angiotensin II type 1 receptor (ATI receptor) in the liver. Meanwhile, the protein expressions of AT1 receptor, transforming growth factor beta 1 (TGF- β1) 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-β1 and PDGF-BB, Serum levels of HA and LN, and MMP-2 activity. Conclusions These results suggest that angiotensin n may play an important role in fibrosis of liver. Perindopril may have a inhibiting effect on CCl4-induced hepatic fibrogenesis of rat.
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