Development of hepatic anti-fibrotic therapy targeted to angiotensin II receptor antagonist-soppression of collagen production in the Ito cell via TGF-β

抗肝纤维化治疗是预防肝硬变的有效方法。2001年，我们进行了一项关于慢性丙型肝炎抗肝纤维化治疗的随机对照研究，但干扰素治疗无效。将30例慢性丙型肝炎患者随机分为两组。15例患者应用血管紧张素II 1型受体拮抗剂氯沙坦50 mg/d治疗3个月。另15例患者为对照组。服药后，肝纤维化标志物--转化生长因子-β-1在氯沙坦组显著降低，而对照组无明显变化。氯沙坦组纤维化面积(%)减少，但意义不大。这一结果提示阻断血管紧张素II信号导致抑制肝纤维化。2002年，血管紧张素II 1型受体拮抗剂(CS-866)应用于大鼠肝硬变模型。治疗组大鼠肝组织转化生长因子-β-1和羟脯氨酸含量明显降低。组织学检查显示，治疗组肝纤维化程度明显低于对照组。

Anti-fibrotic therapy is expcted to prevent hepatic cirrhosis.In 2001, we carried out a randomized controlled study on anti-fibrotic therapy for chronic hepatitis C without effect of interferon therapy. 30 consecutive patients with chronic hepatitis C were randomizedly divided into two groups. 15 patients were treated with losartan (50 mg/day), angiotensin II type 1 receptor antagonist, for 3 months. The other 15 patients were followed as controls. After the oral administration, plasma TGF-β1 concentrations, a marker of fibrosis, significantly decreased in the group of losartan whereas the concentrations did not change in the control group. Fibrosis area (%) in the losartan group was reduced with mild significance. This result suggested that blocking of angiotensin II signal leaded to suppression of heparic fibrosis.In 2002, angiotensin II type 1 receptor antagonist (CS-866) was administered to rat cirrhosis model. The treated rats showed significant decrease in hepatic TGF-β1 and hydroxyproline contents. Histological examination revealed that degree of hepatic fibrosis was much lower in the treated than the controls.