参附配伍对心肌细胞减毒增效作用  

Research progress in roles of ginseng combined with Radix Aconiti Carmichaeli in reducing toxicity and increasing efficiency in myocardial cells

作　　者：李鸿昌 葛运炫 王宁宁 周维 王宇光 马增春 高月 LI Hongchang;GE Yunxuan;WANG Ningning;ZHOU Wei;WANG Yuguang;MA Zengchun;GAO Yue(Qingdao Special Service Sanatorium of PLA Navy,Qingdao Shandong 266071,China;Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]海军青岛特勤疗养中心,山东青岛266071 [2]军事医学研究院辐射医学研究所,北京100850

出　　处：《中国药物警戒》2024年第6期601-605,共5页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2022YFC3500303);国家自然科学基金资助项目(82192911、81630102)。

摘　　要：通过从化学基础、药代动力学、药物代谢、成分间相互作用、生物学机制等方面进行叙述,揭示了参附方配伍的科学内涵。基于用药剂量和分子作用途径发现了参附方的“量-毒-时-效”关系,药效作用主要通过能量代谢途径实现,毒性作用主要是钙超载。分析乌头碱毒效转换窗口,利用基于生理的药代动力学与反向剂量学预测药物组分在体内的毒性阈值,预测中药早期毒性剂量、药物代谢酶和转运体对药物体内过程影响以及药物相互作用等。参附配伍通过药代机制降低乌头碱的浓度,通过毒理机制对抗毒性靶点,起到“七情和合”中的相畏相杀作用。研究初步阐明了参附配伍减毒增效的科学内涵,发展和完善了“七情和合”配伍理论。Objective To study the mechanisms by which ginseng combined with Radix Aconiti Carmichaeli can reduce toxicity while improving efficacy in terms of chemistry,pharmacokinetics,drug metabolism,interactions between components and biological mechanisms.Methods The“dose-toxicity-time-effect”relationship was established based on drug dosage and molecular pathways.Energy metabolism and calcium overload were studied to find out whether they were involved in pharmacological and toxic effects,respectively.The toxicity conversion window of aconitine was analyzed while the toxicity threshold was predicted using physiologically based pharmacokinetic models(PBPK)and in vivo reverse dosimetry.The early toxicity dose of traditional Chinese medicine,impacts of drug metabolic enzymes and transporters on the in vivo disposal process of drugs,and drug interactions were explored.Results It was found that the combination of ginseng with Radix Aconiti Carmichaeli could reduce the concentration of aconitine through pharmacological mechanisms and antagonize toxic targets through toxicological mechanisms,thus acting as both a threat and a killer in the compatibility theory of“seven emotions and harmony”.Conclusion The study has shed light on the role of ginseng combined with Radix Aconiti Carmichaeli in reducing toxicity and increasing efficiency,and contributed to the compatibility theory about the“seven emotions and harmony”.

关 键 词：参附配伍 减毒增效 乌头碱 心肌细胞 药物代谢酶 七情和合 

分 类 号：R994.11[医药卫生—毒理学]