Effects of renin-angiotensin system inhibitors on hepatic fibrosis
- VernacularTitle:肾素-血管紧张素系统与肝纤维化发生
- Author:
Hongshan WEI
;
Dingguo LI
;
Hanming LU
- Publication Type:Journal Article
- Keywords:
Hepatic fibrosis;
Drug therapy;
Renin angiotensin system;
Receptor
- From:
Chinese Journal of Digestion
2001;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective Recently, a series of studies demonstrated that activation of local renin angiotensin system (RAS) may be related to tissue fibrosis, but the role of RAS in hepatic fibrogenesis has not been evaluated. The present study was designed: (1) to assess the effect of angiotensin converting enzyme (ACE) inhibitor and angiotensin Ⅱ type 1 (AT1) receptor antagonist in preventing hepatic fibrosis induced by CCl 4 administration in rats; (2) to investigate whether or not there are expression of AT1 receptors on hepatic stellate cells. Methods Study was conducted in male Sprague Dawley rats. Except for control group, three treated groups, either enalapril (10 mg/kg), losartan (10 mg/kg) or a combination of enalapril and losartan were given to the fibrotic rats (daily gavage), and saline vehicle was given to the control rats. After 6 weeks, liver fibrosis was assessed directly by hepatic morphometric analysis, which have been considered the gold standard for the quantitative measurement of fibrosis. The expression of AT1 receptors and ? smooth muscle actin (? SMA) in liver tissue were detected by immunohistochemical techniques. Results Compared to the rats of control groups, either enalapril or losartan, or a combination of two drugs can limit the expansion of the interstitium ( P 0.05). Expression of AT1 receptors was found in abundance in hepatic fibrotic interstitium of fibrotic rats, whereas only limited in vasculature in rats of control group to a very slight degree. Conclusions The present results demonstrated that: (1) activation of RAS is related to hepatic fibrosis induced by CCl 4; (2) angiotensin converting enzyme inhibitor and AT1 blocker might slow the propression of hepatic fibrosis; (3) activated hepatic stellate cell expresses AT1 receptors.
