丹参粉针剂对二甲基亚硝胺所致大鼠肝纤维化进程的影响

doi:10.5246/jcps.2015.01.007

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (1): 54-62.DOI: 10.5246/jcps.2015.01.007

丹参粉针剂对二甲基亚硝胺所致大鼠肝纤维化进程的影响

杨莹帆^1,2, 孙懿^1*, 赵欣¹, 郑希元¹, 蒲小平¹

1. 北京大学医学部药学院分子与细胞药理学系; 天然药物及仿生药物国家重点实验室, 北京 100191
2. 北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2014-10-08 修回日期:2014-11-13 出版日期:2015-01-15 发布日期:2014-12-10
通讯作者: Tel.: 86-10-82802648

Effects of Salvia miltiorrhiza injectional powder on the development of liver fibrosis initiated by dimethylnitrosamine in rats

Yingfan Yang^1,2, Yi Sun^1*, Xin Zhao¹, Xiyuan Zheng¹, Xiaoping Pu¹

1. Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
2. Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China

Received:2014-10-08 Revised:2014-11-13 Online:2015-01-15 Published:2014-12-10
Contact: Tel.: 86-10-82802648

摘要/Abstract

摘要：

丹参是一种传统的中草药, 对多种疾病有治疗作用, 丹参粉针剂主要由其水溶性成分组成。在本项研究中, 大鼠腹腔注射二甲基亚硝胺诱导肝纤维化, 每周注射3天, 连续4周。在造模2周后, 阳性药组大鼠皮下注射8×10⁵ IU/kg IFNα2b; 各治疗组分别腹腔注射50, 100和200 mg/kg丹参粉针剂, 每周给药6天, 连续4周。结果表明, IFNα2b及3个治疗组的大鼠体重和肝脾比明显增加, 而且3个治疗组大鼠的脾脏指数降低。血清检测结果显示, IFNα2b和丹参粉针剂可降低谷丙转氨酶, 总胆红素, 透明质酸, 和Ⅲ型前胶原水平, 其中100和200 mg/kg剂量组还明显改善了谷草转氨酶、白蛋白水平。在组织学检查中发现, IFNα2b和丹参粉针剂可改善肝细胞的状态, 较少的纤维增生和胶原沉积。免疫组织化学染色显示, IFNα2b和丹参粉针剂显著下调了转化生长因子β1和血小板源性生长因子(PDGF)。总之, 丹参粉针剂对二甲基亚硝胺导致的大鼠肝纤维化具有一定的保护作用, 其机制可能与下调TGF-β1和PDGF有关。

关键词: 丹参, 肝维维化, 二甲基亚硝胺, 转化生长因子-β1, 血小板源性生长因子

Abstract:

Salvia miltiorrhiza (Sm) is a traditional herbal medicine with multiple effects on various diseases. Its water-soluble parts have been used to produce injectional powder. In this study, liver fibrosis rats were induced by intraperitoneal injection of dimethylnitrosamine for 3 consecutive days per week for 4 weeks. After 2 weeks, rats in the positive drug group were subcutaneously injected with 8×10⁵ IU/kg IFNα2b, while the Sm treatment groups were intraperitoneally injected with 50, 100 and 200 mg/kg solution of Sm injectional powder, respectively, for 6 days per week for 4 weeks. The results showed that either IFNα2b or the Sm injectional powder significantly increased the body weight and liver to spleen ratio, and three doses of the powder brought down the spleen index. Serum analysis showed that both IFNα2b and the Sm powder reduced levels of alanine transaminase and total bilirubin, while only 100 and 200 mg/kg of the Sm powder ameliorated aspartate transaminase and albumin levels. In the collagen examination, reduced hyaluronic acid and procollagen type III levels, less fibrous hyperplasia and collagen deposits, and improved hepatocyte states were clearly observed in rats treated with either IFNα2b or Sm injectional powder. In addition, the mechanism of action of the Sm powder was also studied. Immunohistochemical staining showed that IFNα2b and Sm injectional powder significantly down-regulated the expression of transforming growth factor-β1 (TGF-β1) and platelet derived growth factor (PDGF). In conclusion, Sm injectional powder has protective effects on dimethylnitrosamine-initiated liver fibrosis in rats, and the mechanism may include the down-regulation of TGF-β1 and PDGF.

Key words: Salvia miltiorrhiza, Liver fibrosis, Dimethylnitrosamine, Transforming growth factor-β1, Platelet derived growth factor

中图分类号:

R962

Supporting:

杨莹帆, 孙懿, 赵欣, 郑希元, 蒲小平. 丹参粉针剂对二甲基亚硝胺所致大鼠肝纤维化进程的影响[J]. 中国药学(英文版), 2015, 24(1): 54-62.

Yingfan Yang, Yi Sun, Xin Zhao, Xiyuan Zheng, Xiaoping Pu. Effects of Salvia miltiorrhiza injectional powder on the development of liver fibrosis initiated by dimethylnitrosamine in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(1): 54-62.

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丹参粉针剂对二甲基亚硝胺所致大鼠肝纤维化进程的影响

Effects of Salvia miltiorrhiza injectional powder on the development of liver fibrosis initiated by dimethylnitrosamine in rats

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