中国药物警戒 ›› 2013, Vol. 10 ›› Issue (12): 705-708.

• 基础及临床研究 •    下一篇

注射用胡黄连总苷对ConA引起小鼠急性免疫性肝损伤的保护作用研究

王淑娟1,贾志丹2,魏怀玲3,苗露阳3,张丹3,孙华3*   

  1. 1.长春工业大学,吉林长春 130012；
    2.国药一心制药有限公司,吉林长春 130000；
    3.中国医学科学院药物研究所,北京 100050
  • 收稿日期:2013-10-30 修回日期:2016-03-09 出版日期:2013-12-08 发布日期:2016-03-09
  • 通讯作者: 孙华,博士,副研究员,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:王淑娟,女,硕士,制药工程。

Protectiv e Effect of Total Glucoside of for Injection on Concanavalin A-induced Liver Injury in Mice

WANG Shu-juan1, JIA Zhi-dan2, WEI Huai-ling3, MIAO Lu -yang3, ZHANG Dan3 ,SUN Hua3*   

  1. 1.Institute of Chemical Engineering, Changchun University of Technology, Jilin Changchun 130012, China;
    2.Sinopharm A-Think Pharmaceutical Co.,Ltd, Jilin Changchun 130000, China;
    3.Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2013-10-30 Revised:2016-03-09 Online:2013-12-08 Published:2016-03-09

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摘要： 目的 利用ConcanavalinA（ConA）引起的免疫性肝损伤模型,对注射用胡黄连总苷的保肝活性和量效关系进行研究。方法 注射用胡黄连总苷静脉给予ICR小鼠（0.5～8mg·kg-1×5）,于末次给药后2h,动物尾静脉ConA 20mg·kg-1建立急性免疫性肝损伤模型,16h后处理动物,制备血清,全自动生化分析仪检测血清ALT,AST及LDH水平,H.E.染色考察肝脏病理状态。结果 ConA20mg·kg-1能引起小鼠显著的急性免疫性肝损伤,血清ALT,AST及LDH含量均显著升高,肝组织出现以炎症细胞浸润、肝细胞坏死为主要特征的病理改变。注射用胡黄连总苷0.5～4mg·kg-1剂量对ConA引起的肝损伤有显著保护作用,明显降低血清转氨酶水平,改善肝脏病理状态,其中1mg·kg-1剂量药效最佳,8mg·kg-1剂量药效有所下降,但此剂量未显示明显毒性。结论 注射用胡黄连总苷对ConA引起的免疫性肝损伤有明确的保护作用,其起效剂量低,高于8mg·kg-1活性下降,在临床实验时需注意剂量的选择问题。

关键词: 胡黄连, 总苷, 注射液, ConA, 肝损伤

Abstract: Objective To study the protective effect of total glucoside (TGP) for infection on Concanavalin A(ConA)-induced acute liver injury in ICR mice. Methods ICR mice were given intravenously TGP injection 0.5～8mg·kg-1 for five days(one time/day). After the last administration 2h, the mice were injected intravenously ConA 20mg·kg-1 to establish the immunological liver damage model. All animals were killed on 16h after ConA treatment. The activities of ALT, AST and LDH were measured by automatic chemistry analyzer(TBA-40FR). Liver histopathological changes were examined by H.E. and light microscopy. Results ConA 20mg·kg-1 could induced significant liver damage, expressed in the higher serum ALT,AST,LDH activities and the apoptosis or inflammatory cell infiltration in liver tissue. TGP injection 0.5～4mg·kg-1 showed significantly protective effect to liver damage induced by ConA, which could reduce serum transaminase activities and prevent the pathological injury. The optimum dose is 1mg·kg-1. There wasa reduced efficacy when the dose is 8mg·kg-1. While at this dose, there are no obvious toxicity. Conclusion TGP injection showed a significant protective effect on ConA-induced liver injury in mice. Its effective dose is low and the therapeutic activity will cut down when the dose is higher than 8mg·kg-1. It should be careful to the dose choice in clinical trial.

Key words: total glucosides, injection, Con A, liver injury

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