Tuncer Ilyas, Ozbek Hanefi, Ugras Serdar, Bayram Irfan
Department of Gastroenterology, Yuzuncu Yil University Medical Faculty, Van, Turkey.
Exp Toxicol Pathol. 2003 Sep;55(2-3):159-66. doi: 10.1078/0940-2993-00309.
BACKGROUND/AIM: Angiotensin converting enzyme (ACE) and angiotensin II (AT-II) have been suggested to play an important role in liver fibrogenesis. There is a significant relationship between inheritance of hightened expression of transforming growth factor beta1 (TGF-beta1) and AT-II and the development of progressive hepatic fibrosis. The purpose of this study was to investigate the effects of captopril, an ACE inhibitor and candesartan cilexetil, an AT-II type 1 receptor (AT1-R) blocker, on liver fibrosis induced in rats by carbon tetrachloride (CCl4) administration.
rats were divided into 4 experimental groups: The first group was given CCl4 alone; the second was given both CCl4 and captopril (100 mg x kg(-1) x day(-1)); the third was given both CCl4 and candesartan cilexetil (8 mg x kg(-1) x day(-1)); fourth group was given 0.9% NaCl only. Seven weeks after initiating the treatment, indices of fibrosis were assessed.
Candesartan cilexetil treatment significantly reduced the fibrosis development. These inhibitory effects were not observed in the captopril-treated group. The mean fibrosis score was significantly lower in the CCl4/candesartan group compared with the group applied to CCl4 alone and the group applied to CCl4/captopril. Similarly, the number of alpha-smooth muscle actin positive cells was markedly suppressed by candesartan treatment.
The results suggest that AT-II plays a pivotal role in hepatic fibrogenesis and candesartan significantly attenuates the progression of liver fibrosis. This drug may provide an effective new strategy for prevention of liver fibrosis. Its effectiveness should be investigated in chronic liver disease associated with progressive fibrosis.
背景/目的：血管紧张素转换酶（ACE）和血管紧张素II（AT-II）被认为在肝纤维化形成过程中起重要作用。转化生长因子β1（TGF-β1）和AT-II高表达的遗传与进行性肝纤维化的发展之间存在显著关系。本研究旨在探讨ACE抑制剂卡托普利和AT-II 1型受体（AT1-R）阻滞剂坎地沙坦酯对四氯化碳（CCl4）诱导的大鼠肝纤维化的影响。
将大鼠分为4个实验组：第一组仅给予CCl4；第二组给予CCl4和卡托普利（100 mg·kg-1·d-1）；第三组给予CCl4和坎地沙坦酯（8 mg·kg-1·d-1）；第四组仅给予0.9%氯化钠。治疗7周后，评估纤维化指标。
坎地沙坦酯治疗显著降低了纤维化的发展。在卡托普利治疗组未观察到这些抑制作用。与仅应用CCl4的组和应用CCl4/卡托普利的组相比，CCl4/坎地沙坦组的平均纤维化评分显著更低。同样，坎地沙坦治疗显著抑制了α-平滑肌肌动蛋白阳性细胞的数量。
结果表明，AT-II在肝纤维化形成中起关键作用，坎地沙坦显著减轻肝纤维化的进展。该药物可能为预防肝纤维化提供一种有效的新策略。其有效性应在与进行性纤维化相关的慢性肝病中进行研究。
