中国药物警戒 ›› 2015, Vol. 12 ›› Issue (8): 449-453.

• 基础研究 •    下一篇

附子对脾肾阳虚型心衰大鼠的效-毒关联评价

李晓宇1, 栾永福2, 孙蓉1   

  1. 1. 山东省中医药研究院,山东 济南250014;
    2. 山东省食品药品检验研究院,山东 济南250101
  • 收稿日期:2015-09-02 修回日期:2015-09-02 出版日期:2015-08-08 发布日期:2015-09-02
  • 通讯作者: 孙蓉,博士,研究员·博导,中药药理与毒理研究。E-mail：sunrong107@163.com
  • 作者简介:李晓宇,硕士,实习研究员,中药毒理与神经药理研究。
  • 基金资助:
    国家重点基础研究发展计划（973）; 中医基础理论专项资助项目课题2（2009CB522802）

Evaluation on the "Efficacy-toxicity" Correlation of Radix Aconiti Lateralis Praeparata on Spleen-kidney Yang Deficiency Rat with Heart Failure

LI Xiao-yu1, LUAN Yong-fu2, SUN Rong1   

  1. 1. Shandong Academy of Chinese Medicine, Shandong Ji'nan 250014, China;
    2. Shandong Institude for Food and Drug Control, Shandong Ji'nan 250101, China
  • Received:2015-09-02 Revised:2015-09-02 Online:2015-08-08 Published:2015-09-02

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摘要： 目的 通过附子水煎剂对脾肾阳虚型心衰大鼠“强心”功效及心脏毒性的研究,探讨附子在大鼠病证结合模型上针对心脏靶器官的功效-毒性表达的关联性。方法 采用皮下注射异丙肾上腺素建立大鼠慢性心力衰竭模型,灌胃大黄粉悬液建立脾肾阳虚模型;造模同时灌胃不同剂量的附子水煎剂,连续9 d。测试各组大鼠实验前后的心电图和血流动力学,对大鼠心、左心室、脑、肝、脾和肾称重并计算脏器系数,检测血清中N末端脑钠钛前体（NT-pro BNP）、高敏C反应蛋白（hs-CRP）、天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）和心肌肌钙蛋白（cTn-I）的活力。结果 附子水煎剂在1.35~5.40 g·kg-1能显著抑制脾肾阳虚型心衰大鼠的T波升高、心率减慢和QRS间期延长（P <0.05）,升高脾肾阳虚型心衰型大鼠的LVSP、±dp/dtmax和血清中AST、LDH和cTn-I的水平（P <0.05）,并能降低LVEDP和血清中NT-pro BNP、hs-CRP的水平（P <0.05）,增大心系数和左心室系数（P <0.05）,并呈现一定的剂量依赖性。结论 附子水煎剂在1.35~5.40 g·kg-1剂量范围内,对脾肾阳虚型心衰大鼠的“温补脾阳”、“回阳救逆”的功效表达同时也表达了心脏毒性,提示附子基于心脏的“效-毒”关联评价对保证附子临床强心功效的安全应用有重要的意义。

关键词: 附子, 脾肾阳虚, 心衰, 功效, 毒性

Abstract: Objective The efficacy and heart toxicity of Aconite's water decoction on spleen-kidney yang deficiency rat with heart failure were studied to explore "efficacy-toxicity" relationship of Aconite on animal models combined disease and syndrome. Methods Chronic heart failure rat model was established with isoprenaline by subcutaneous injection and spleen-kidney yang deficiency rat model was established with rhubarb powder suspension. Rat models were established and Aconite's water decoction was administered simultaneously for 9 consecutive days. Electrocardiogram (ECG) and hemodynamics of rats were measured. Heart, left ventricular, brain, liver, spleen and kidney were weighed and indexes of them were calculated. The activities of N-terminal pro-brain natriuretic peptide (NT-pro BNP), high sensitivity C reactive protein (hs-CRP), aspartate transaminase (AST), lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I) were detected. Results The heart rate of rats dropped, the amplitude of T enlarged and QRS extended after the administration of Aconite's water decoction in the dosage range of 1.35~5.40 g·kg-1. Left ventricular pressure (LVSP) and left ventricular pressure development during isovolumetric contraction/relaxation(±dp/dtmax) elevated and the levels of serum NT-pro BNP and hs-CRP reduced. Heart index and left ventricular index increased. Conclusion Aconite's water decoction in the dosage range of 1.35~5.40 g·kg-1 has certain efficacy on spleen-kidney yang deficiency rat with heart failure, showing that the evaluation on the "efficacy-toxicity" correlation of Radix Aconiti Lateralis has important significance to ensure the safety of clinical cardiac function.

Key words: Radix Aconiti Lateralis Praeparata, spleen-kidney yang deficiency, heart failure, efficacy, toxicity

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