[Effect of ACE-I and AT-1 receptor blocker on the progression of CCl(4)-inducing rat hepatic fibrogenesis].

OBJECTIVE

The aim of the present study was to determine the effects of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat hepatic fibrosis induced by CCl4.

METHODS

60 male wistar rats weighting about 250 g were divided into 4 groups. Model group (Mo): The rats were injected with 40% CCl(4) 0.25 ml/100 g subcutaneously three times a week. Perindopril group (Pe): The rats were injected with 40% CCl(4). Perindopril, equivalent to 2 mg x kg(-1) x d(-1), was given i.g. Losartan group (Lo): The rats were injected with 40% CCl(4). Losartan, equivalent to 50 mg x kg(-1) x d(-1), was given i.g. 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 AT-1 receptor in the liver. Meanwhile, the protein expressions of AT-1 receptor, TGF-beta1 and 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 radioimmunoassays.

RESULTS

RT-PCR and Western blot revealed that there was a up-regulation in AT-1 receptor expression in model group compared with control group. Both of perindopril and losartan 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 IImay play an important role in fibrosis of liver. Perindopril and losartan may have inhibiting effects on CCl(4)-induced hepatic fibrogenesis of rat.