中国中药杂志

2011, v.36(24) 3506-3510

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大黄用于治疗大鼠实验性黄疸的日服用次数初步研究
Primary research on daily administration times of rhubarb used to treat experimental jaundice in rats

吕俊兰;付珊珊;郭静静;刘永;袁海龙;肖小河;
LV Junlan1,2,FU Shanshan1,2,GUO Jingjing1,2,LIU Yong1,2,YUAN Hailong1,XIAO Xiaohe1 (1.302 Military Hospital of China,Beijing 100039,China; 2.Chengdu University of Traditional Chinese Medicine,Chengdu 611730,China)

摘要(Abstract):

目的:研究大黄用于治疗大鼠实验性黄疸(胆汁淤积型肝炎)时的日服次数,验证前期已建立以效应动力学为核心、成分药动学为辅佐,也即是基于PD-PK的中药日服用次数研究模式的正确性与可行性,并继续完善大黄日服用次数研究方法与模式。方法:采用4%ANIT造成大鼠高黄疸模型,48 h后分别每日灌服大黄提取物3.6 g.kg-11次、1.8 g.kg-12次和1.2 g.kg-13次,观察8 h内胆汁流量变化;眼眶后静脉取血,用于测定其不同时间点的血清生化指标TBIL,ALT,ALP,AST,GGT值及大鼠血中移行成分大黄酸浓度。分别以生物效应值(胆汁流量、血清生物学指标)和血中移行成分含量为指标,得到各自时-效曲线和时-量曲线。综合分析时-量关系和时-效关系,制定大黄用于治疗大鼠实验性黄疸时合理的日服用次数。结果:每日给药2次时,8 h内胆汁总量分别是每日给药1次、每日给药3次的1.56倍和1.7倍;而8 h时TBIL值分别是每日给药1次和3次的23%,22%,ALT值分别是每日给药1次和3次的86%,65%,ALP值分别是每日给药1次和3次的50%,71%;AST,GGT值无显著影响;每日给药2次时,大黄酸血药浓度水平最高且能够较长时间维持较高水平,这可能正是大黄发挥显著药理作用的主要原因。结论:前期建立的以效为核心,成分药动学为辅助的方法用于研究中药的日服次数科学可行;大黄用于治疗胆汁淤积型肝炎(黄疸)时,以每日服用2次为佳。
Objective: To study the rational daily administration times of rhubarb when it is used to treat experimental jaundice in rats,at the same time,validate the accuracy and feasibility of the method which was previously established to research the rational daily administration times of rhubarb(PD-PK method),and consummate it.Method: After the rats were modeled by 4% ANIT(75 mg·kg-1) for two days,rhubarb extraction was drenched 3.6 g·kg-1once a day,1.8 g·kg-1 twice a day and 1.2 g·kg-1 three times a day,respectively.Then the total bile and the flow rate of bile were observed.Blood was collected from the veins behind the eye sockets after different intervals and was used to investigate the biochemical indexes of the blood serum,such as TBIL,ALT,ALP,AST and GGT,and to determine the concentration of rheic acid in the blood plasma,then the time-effect curve and time-dose curve were obtained.The rational daily administration times of rhubarb was determined when it was used to treat experimental jaundice based on the comprehend analysis of time-effect and time-concentration relationships.Result: Compared with the groups which were administered once a day and three times a day,the total bile within 8 h of the rats which were administered twice a day was 1.56 and 1.7 times higher,respectively,while the TBIL was 23%,22%,and ALT was 86%,65% of the other two,ALP was 50%,71% of the other two,respectively.With administrated twice a day,the blood concentration of rheic acid could maintain a high level for a longer time,which maybe the main reason for its effect.Conclusion: The method based on pharmacodynamics and pharmacokinetics is scientific and feasible to study the rational daily administration times of traditional Chinese medicine.Rhubarb is better to administrate two times a day to treat jaundice.

关键词(KeyWords): 大黄;大鼠;实验性黄疸;日服次数
rhubarb;rats;experimental jaundice;daily administration times

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81073069);; 国家“重大新药创制”科技重大专项(2009ZX09502-022)

作者(Authors): 吕俊兰;付珊珊;郭静静;刘永;袁海龙;肖小河;
LV Junlan1,2,FU Shanshan1,2,GUO Jingjing1,2,LIU Yong1,2,YUAN Hailong1,XIAO Xiaohe1 (1.302 Military Hospital of China,Beijing 100039,China; 2.Chengdu University of Traditional Chinese Medicine,Chengdu 611730,China)

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