Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells
文献类型：期刊论文
| 作者 | Zhao, Xin-Yan1; Zeng, Xin2,3; Li, Xin-Min1; Wang, Tai-Ling4; Wang, Bao-En1 |
| 刊名 | Clinical and experimental pharmacology and physiology
 |
| 出版日期 | 2009-10-01 |
| 卷号 | 36期号:10页码:963-968 |
| 关键词 | Antifibrotic therapy Fibrosis stage Human hepatic stellate cells Liver fibrosis Pirfenidone |
| ISSN号 | 0305-1870 |
| DOI | 10.1111/j.1440-1681.2009.05194.x |
| 通讯作者 | Wang, bao-en(wangbbee@126.com) |
| 英文摘要 | P>pirfenidone (pfd; 5-methyl-1-phenyl-2(1h)-pyridone) is an effective and novel agent with antifibrotic and anti-inflammatory properties. in the present study, we investigated the antifibrotic effects of pfd on experimental liver fibrosis models in rodents and the possible underlying molecular mechanisms. liver fibrosis was induced by carbon tetrachloride (ccl(4)) in balb/c mice. pirfenidone (250 mg/kg) and silymarin (50 mg/kg) were given to different groups of rats by gastric gavage for 4 weeks. pirfenidone significantly attenuated fibrosis severity, as determined by histopathological scores and hydroxyproline levels in liver tissue, by 49.8 and 44.9%, respectively, compared with the ccl(4)-treated group. the antifibrotic effects of pfd were significantly greater than those of silymarin, as indicated by a decrease of 23.5 and 24.8% in histopathological scores and hydroxyproline levels, respectively. liver fibrosis was also induced by albumin antigen-antibody complex in wistar rats, which were then treated with the same doses of pfd and silymarin for 8 weeks. pirfenidone significantly reduced the degree of fibrosis compared with ccl(4)-treated rats (by 45.0 and 51.0% as determined by histopathological scores and hydroxyproline levels in liver tissue, respectively). the antifibrotic effects of pfd were comparable to those of silymarin. the effects of pfd on the expression of extracellular matrix-associated genes in human hepatic stellate cells (the lx-2 cell line) were measured by real-time quantitative polymerase chain reaction. lx-2 cells were treated with or without 100 mu mol/l or 1 mmol/l pfd for 24 h. pirfenidone significantly inhibited the expression of a-smooth muscle actin and type i collagen in 8 ng/ml transforming growth factor-beta 1- or 5% fetal bovine serum-activated lx-2 cells in a dose-dependent manner. in conclusion, the results of the present study demonstrate that pfd is effective in ameliorating fibrogenesis induced by ccl(4) in mice and by the albumin complex in rats. these effects were mediated mainly via inhibition of the activation of hepatic stellate cells, as well as antifibrotic actions (i.e. inhibition of collagen synthesis) of pfd. |
| WOS关键词 | CIRRHOSIS ; INJURY ; RATS |
| WOS研究方向 | Pharmacology & Pharmacy ; Physiology |
| WOS类目 | Pharmacology & Pharmacy ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000271001700006 |
| 出版者 | WILEY-BLACKWELL PUBLISHING, INC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2394369 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Wang, Bao-En |
| 作者单位 | 1.Capital Med Univ, Beijing Friendship Hosp, Liver Res Ctr, Beijing 100050, Peoples R China 2.Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 4.China Japan Friendship Hosp, Dept Pathol, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Xin-Yan,Zeng, Xin,Li, Xin-Min,et al. Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells[J]. Clinical and experimental pharmacology and physiology,2009,36(10):963-968. |
| APA | Zhao, Xin-Yan,Zeng, Xin,Li, Xin-Min,Wang, Tai-Ling,&Wang, Bao-En.(2009).Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells.Clinical and experimental pharmacology and physiology,36(10),963-968. |
| MLA | Zhao, Xin-Yan,et al."Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells".Clinical and experimental pharmacology and physiology 36.10(2009):963-968. |
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来源：中国科学院大学
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