Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

作     者：Fabio Marra Raffaella DeFranco Gaia Robino Erica Novo Eva Efsen Sabrina Pastacaldi Elena Zamara Alessandro Vercelli Benedetta Lottini Carlo Spirli Mario Strazzabosco Massimo Pinzani Maurizio Parola 

作者机构：Dipartimento di Medicina Interna and Center for ResearchTransferand High Education ‘DENOTHE'University of FlorenceItaly Dipartimento di Medicina e Oncologia SperimentaleUniversity of TurinItaly Benedetta LottiniMassimo PinzaniDipartimento di Medicina Interna and Center for ResearchTransferand High Education ‘DENOTHE'University of FlorenceItaly Dipartimento di AnatomiaFarmacologia e Medicina LegaleUniversity of TurinItaly Istituto Veneto di Medicina MolecolarePaduaItaly 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2005年第11卷第32期

页      面：4931-4938页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by the Italian MIUR Grant  No. MM_06315722 by the University of Florenceby the Italian Liver Foundation. Eva Efsen was Supported in Part by the Tode Travel Grant  the Direktφr Madsen's GrantFhv. Direktφr Nielsen's Grant (Denmark) 

主　　题：Cholangiocytes Ductular reaction PPAR-γ Hepatic stellate cells Myofibroblasts Troglitazone 

摘      要：AIM： To investigate the effects of troglitazone （TGZ）, an anti-diabetic drug which activates peroxisome proliferatoractivated receptor-y （PPAR-y）, for liver tissue repair, and the development of ductular reaction, following common bile duct ligation （BDL） in rats. METHODS： Rats were supplemented with TGZ （0.2% w/w in the pelleted food） for i wk before BDL or sham operation. Animals were killed at 1, 2, or 4 wk after surgery. RESULTS： The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type I gene expression and liver hydroxyproline levels. Accumulation of a-smooth-muscle actin （SMA）-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells （HSC） and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of γ-glutamyltransferase （GGT）. CONCLUSION： Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.