Fujita Koji, Yoneda Masato, Wada Koichiro, Mawatari Hironori, Takahashi Hirokazu, Kirikoshi Hiroyuki, Inamori Masahiko, Nozaki Yuichi, Maeyama Shiro, Saito Satoru, Iwasaki Tomoyuki, Terauchi Yasuo, Nakajima Atsushi
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Japan.
Dig Dis Sci. 2007 Dec;52(12):3455-64. doi: 10.1007/s10620-007-9741-4. Epub 2007 Apr 5.
The term nonalcoholic steatohepatitis (NASH) has recently been proposed to identify a fatty liver disease accompanied by diffuse fatty infiltration and inflammation. However, no drug therapy has been established for NASH as yet. In the present study, we demonstrate the effect of the angiotensin II type 1 receptor antagonist telmisartan on the development of NASH in a rat model. Telmisartan, but not the angiotensin receptor antagonist valsartan, markedly attenuated hepatic steatosis, inflammation, and fibrosis in these rats. The quantitative parameters of steatosis, inflammation, and fibrosis were also ameliorated by treatment with telmisartan. Compared with telmisartan, the peroxisome proliferator-activated receptor-gamma agonist pioglitazone attenuated hepatic steatosis and fibrosis of the liver to a similar degree. However, telmisartan, but not pioglitazone, dramatically decreased both subcutaneous and visceral fat. In conclusion, these results indicated that telmisartan should be the drug of first choice for the treatment of patients with NASH.
术语非酒精性脂肪性肝炎（NASH）最近被提出用于识别一种伴有弥漫性脂肪浸润和炎症的脂肪性肝病。然而，目前尚未确立针对NASH的药物治疗方法。在本研究中，我们证明了血管紧张素II 1型受体拮抗剂替米沙坦在大鼠模型中对NASH发展的影响。替米沙坦而非血管紧张素受体拮抗剂缬沙坦，显著减轻了这些大鼠的肝脏脂肪变性、炎症和纤维化。替米沙坦治疗也改善了脂肪变性、炎症和纤维化的定量参数。与替米沙坦相比，过氧化物酶体增殖物激活受体γ激动剂吡格列酮在相似程度上减轻了肝脏脂肪变性和纤维化。然而，替米沙坦而非吡格列酮显著减少了皮下和内脏脂肪。总之，这些结果表明替米沙坦应是治疗NASH患者的首选药物。
