中国药物警戒 ›› 2014, Vol. 11 ›› Issue (8): 453-456.

• 基础与临床研究 • 上一篇    下一篇

注射用胡黄连总苷对α-萘异硫氰酸酯诱发小鼠胆汁淤积性黄疸的保肝退黄作用

梁晓东1, 张丽2, 贾志丹1, 魏怀玲3, 鲍秀琦3, 张丹3, 孙华3*   

  1. 1国药一心制药有限公司北京研发中心,北京 100176;
    2北京航天中心医院老年医学二科,北京 100041;
    3中国医学科学院药物研究所,北京 100050）、
  • 收稿日期:2016-02-03 修回日期:2016-02-03 出版日期:2014-08-08 发布日期:2016-03-02
  • 通讯作者: 孙华,博士,副研究员·硕士生导师,肝脏生化药理学及肿瘤多药耐药性。E-mail：sunhua@imm.ac.cn
  • 作者简介:梁晓东,男,博士,副研究员,新药研发。

Effects of Total Glucoside of on Intrahepatic Cholestasis in Mice Induced by α-Naphthylisothiocyanate

LIANG Xiao-Dong1, Zhang Li2 ,JIA Zhi-Dan1, WEI Huai-Ling3 ,BAO Xiu-Qi3, ZHANG Dan3 ,SUN Hua3*   

  1. 1Beijing R&DCenter, SinopharmA-Think Pharmaceutical Co.,Ltd, Beijing 100176, China;
    2Aerospace Center Hospital,Beijing 100041, China;
    3Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2016-02-03 Revised:2016-02-03 Online:2014-08-08 Published:2016-03-02

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摘要： 目的 利用α
-萘异硫氰酸酯（α
-Naphthylisothiocyanate, ANIT）引起的胆汁淤积性肝损伤模型,考察注射用胡黄连总苷的保肝退黄活性。方法 注射用胡黄连总苷静脉注射给予ICR小鼠（0.33~9mg·
kg-1,1次/天×
5天）,在第3次给药后2 h口服给予ANIT 80 mg·
kg-1一次,建立胆汁淤积性黄疸模型。末次给药后2 h处理动物,制备血清,全自动生化分析仪检测血清ALT、AST、ALB、ALP、TBIL、DBIL及TBA水平,H.E.染色考察肝脏病理状态。结果 ANIT 80 mg·
kg-1引起小鼠显著的肝损伤及黄疸,血清ALT、AST、ALP、TBIL、DBIL及TBA水平均显著升高,肝组织细胞凋亡、胆管细胞受损。注射用胡黄连总苷0.33~9 mg·
kg-1对ANIT引起的胆汁淤积性黄疸具显著的阻抑活性,能够降低血清转氨酶水平和胆红素及胆汁酸水平,改善肝脏病理状态。0.33~3 mg·
kg-1剂量范围内显示一定量效关系。结论 注射用胡黄连总苷在0.33~9 mg·
kg-1范围内对ANIT引起的小鼠黄疸具显著的保肝退黄作用,1~3 mg·
kg-1剂量范围内活性最佳,值得临床试验参考。

关键词: 胡黄连, 总苷, 注射液, α, -萘异硫氰酸酯, 肝损伤, 胆汁淤积

Abstract: Objective To investigate the protective effects of total glucoside of Picrorhiza scrophulariflora (TGP) on intrahepatic cholestasis induced by α-naphthylisothiocyanate (ANIT) in ICR mice. Methods TGP (0.33~9 mg·kg-1 per day) were injectively given to experimental mice for five consecutive days. A single dose of ANIT (80 mg·kg-1) was orally given to mice on the third day to induce intrahepatic cholestasis. All animals were killed on 2 h after TGP final administration. The levels of serum ALT,AST,ALB,ALP,TBIL,DBIL and TBA were measured by automatic chemistry analyzer (TBA-40FR). Liver histopathological changes were examined by H.E and light microscopy. Results ANIT 80 mg·kg-1 could induced significant liver damage and jaundice, expressed in the higher serum ALT,AST,ALP,TBIL,DBIL,TBA activities and the apoptosis or bile canaliculus injury in liver tissue. TGF injection (0.33~9 mg·kg-1) showed significantly protective effects to liver damage and jaundice induced by ANIT. Compared with the model group, TGP could significantly reduce the elevated serum ALT,AST,ALP,TBIL,DBIL,TBA and relieve the liver pathological injury. There is a dose-dependent relationship between 0.33~3 mg·kg-1 dose range. Conclusion TGP injection showed the significant action of reducing serum bilirubin and transaminase and improving liver tissue injury of experimental cholestasis induced by ANIT. The optimum doses are 1~3 mg·kg-1. It should be careful to make the dose choice in clinical trial.

Key words: Picrorhiza scrophulariflora Pennell, total glucosides, injection, ANIT, liver injury, cholestasis

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