Telmisartan improves nonalcoholic steatohepatitis in medaka (Oryzias latipes) by reducing macrophage infiltration and fat accumulation

被引:35
作者
Kuwashiro, Shinya [1 ]
Terai, Shuji [1 ]
Oishi, Toshiyuki [1 ]
Fujisawa, Koichi [1 ]
Matsumoto, Toshihiko [1 ]
Nishina, Hiroshi [2 ]
Sakaida, Isao [1 ]
机构
[1] Yamaguchi Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Yamaguchi 7558505, Japan
[2] Tokyo Med & Dent Univ, Dept Dev & Regenerat Biol, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
Nonalcoholic steatohepatitis; Telmisartan; Macrophage; Apoptosis; Medaka; Oryzias latipes (Teleostei); ACTIVATED RECEPTOR-GAMMA; ENZYME-ALTERED LESIONS; LIVER-DISEASE; INFLAMMATION; FIBROSIS; MODEL; CCR2;
D O I
10.1007/s00441-011-1132-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We investigated the efficacy of the antihypertensive drug telmisartan (Tel) and the mechanisms underlying the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) in a medaka (Oryzias latipes) NASH model. We used the NASH activity score (NAS) developed in humans to assess the histology of the medaka NASH model and found that NAS increased with time. Further, TUNEL-positive apoptosis hepatocytes were found in the medaka NASH model. Tel administration resulted in the increased expression of liver peroxisome proliferator-activated receptor-gamma, carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 and decreased the number of 8-hydroxydeoxyguanosine-positive hepatocytes and the migration of macrophages positive for diastase-periodic-acid-Schiff. Medaka NAS was improved by Tel administration but fatty acid content was not affected. Tel reduced the infiltration of macrophages into the liver and ameliorated NASH pathology.
引用
收藏
页码:125 / 134
页数:10
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