中国药物警戒 ›› 2021, Vol. 18 ›› Issue (7): 632-636.
DOI: 10.19803/j.1672-8629.2021.07.08

• 基础与临床研究 • 上一篇    下一篇

参附配伍后附子在心力衰竭大鼠体内的药代动力学研究

谢光辉1, 马增春1, 梅雨1, 张雪梅1,2, 谭洪玲1, 高月1,*   

  1. 1军事医学研究院辐射医学研究所,北京 100850;
    2广东药科大学,广东 广州 510573
  • 收稿日期:2021-04-21 出版日期:2021-07-15 发布日期:2021-07-23
  • 通讯作者: *高月,女,研究员,药理学。E-mail：gaoyue@bmi.ac.cn
  • 作者简介:谢光辉,男,在读硕士,药理药代研究。
  • 基金资助:
    国家自然科学基金重点项目(81630131); 国家自然科学基金面上项目(81673633)

Evaluation of Pharmacokinetics of Aconiti Lateralis Radix of Shenfu Prescription in Rats with Heart Failure

XIE Guanghui1, MA Zengchun1, MEI Yu1, ZHANG Xuemei1,2, TAN Hongling1, GAO Yue1,*   

  1. 1Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China;
    2Guangdong Pharmaceutical University, Guangzhou Guangdong 510573, China
  • Received:2021-04-21 Online:2021-07-15 Published:2021-07-23

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摘要： 目的 研究参附配伍后附子在心力衰竭大鼠体内的药代动力学,为参附配伍减毒增效提供数据支持。方法 SD大鼠40只,雌雄各半,建立并评价心力衰竭大鼠模型;手术后,SD大鼠分为3组,正常组、模型组和模型+红参组,开展药代动力学研究,各组大鼠1.0 g/kg灌胃给药附子提取液,于给药前和给药后0.25、0.5、1、2、4、8、12、24和48 h时间点采集血样，利用UPLC-MS/MS测定血药浓度，并利用DAS软件进行药代动力学参数的计算分析。结果 模型组大鼠评价显示，血清中心衰标志物显著升高，心脏重量系数明显升高，病理学观察到心肌细胞有大面积死亡、心肌纤维间隙增宽现象，模型建立成功。药代动力学参数结果表明，相比于正常状态，模型组大鼠体内的乌头碱和次乌头碱的AUC0~48 h显著降低，终末端半衰期（t1/2z）有明显的缩短；与模型组对比，模型+红参组的AUC0~48 h升高，t1/2z延长。结论 附子在心力衰竭大鼠体内吸收较差，代谢速率较快，体内滞留时间短，红参能够显著改善附子在体内的代谢过程，增加附子体内吸收，延长作用时间，从而增加疗效。

关键词: 附子, 液相色谱-质谱联用技术, 人参, 心力衰竭, 药代动力学

Abstract: Objective To study the pharmacokinetics of Aconiti Lateralis Radix of Shenfu prescription in rats with heart failure and provide data for toxicity reduction and enhanced efficacy of Ginseng and Aconiti Lateralis Radix. Methods An animal model with heart failure was established and evaluated in 40 SD rats (half male and half female). After surgery, SD rats were divided into three groups: normal, model and M+ginseng groups. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h after oral administration of Fuzi extracts. UPLC-MS/MS was used for determination of blood drug concentrations while DAS software was used to analyze pharmacokinetic parameters. Results Evaluation of the model group showed that the heart failure markers in serum of rats were significantly higher. The coefficient of cardiac weight was increased. Meanwhile, mass death of myocardial cells was observed and the space between myocardial fibers was wider pathologically, suggesting that the establishment of the model was successful. The results of pharmacokinetic parameters showed that the AUC (0~48 h) became much smaller and t1/2z of AC and HA was significantly shortened in the model group compared with the normal group. In addition, compared to the model group, the AUC (0~48 h) and t1/2z of the M+ginseng group were increased. Conclusion The absorption of aconitum alkaloids in rats with heart failure is poor but the metabolic rate is faster, leading to a short retention time. Ginseng could improve the metabolic process of aconitum alkaloids in vivo significantly, which means better absorption and a longer action time. This may be the reason that the efficacy is enhanced.

Key words: aconiti lateralis radix, UPLC-MS/MS, ginseng, heart failure, pharmacokinetics

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