川芎提取物改善曲妥珠单抗诱导心肌细胞损伤的药效物质研究  

Pharmacoactive Substances of Chuanxiong Rhizoma Extract in Ameliorating Trastuzumab-Induced Myocardial Cell Injury

作　　者：杨家慧 徐静 刘欣桐 曹波 余诺贤 张铭予 范林林 李春雨 李国辉 YANG Jiahui;XU Jing;LIU Xintong;CAO Bo;YU Nuoxian;ZHANG Mingyu;FAN Linlin;LI Chunyu;LI Guohui(Dept.of Pharmacy,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Dept.of Pharmacy,the First Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院药剂科,北京100021 [2]中国医科大学附属第一医院药学部,沈阳110001

出　　处：《中国医院用药评价与分析》2025年第3期282-288,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：北京市自然科学基金资助项目(No.L248025)。

摘　　要：目的:探讨川芎提取物改善曲妥珠单抗相关心脏毒性药效的物质基础。方法:应用均匀设计和体外保护心肌细胞损伤的生物活性检测方法,结合化学指纹图谱进行谱效相关分析,探索川芎提取物改善曲妥珠单抗诱导心肌细胞损伤的药效成分。结果:均匀设计法优化结果显示,川芎最佳醇提取工艺为75%乙醇,9倍溶剂量,乙醇浸润35 min,超声提取30 min;均匀设计下的1—9号样本提取物均可改善曲妥珠单抗诱导的心肌细胞损伤,保护作用最强的为3号样本(EC_(50)=0.037),最弱的为2号样本(EC_(50)=0.317)。谱效相关分析结果表明,川芎嗪、洋川芎内酯I、阿魏酸和正丁基苯酞等4个成分具有相关性,其中相关性最强的为川芎嗪(r=0.68,P<0.05)。验证实验结果显示,川芎嗪活性最强,其次为阿魏酸、正丁基苯酞和川芎内酯I,与谱效相关分析结果基本一致。结论:醇提取方法能够影响川芎改善曲妥珠单抗诱导心肌细胞损伤的药效物质含量变化;川芎嗪、洋川芎内酯I、阿魏酸和正丁基苯酞为川芎提取物改善曲妥珠单抗诱导心肌细胞损伤的主要药效成分。本研究可为中药改善抗肿瘤药物相关心脏毒性的药效物质及关联临床疗效的质量控制方法提供科学依据。OBJECTIVE:To explore the underlying mechanism of Chuanxiong rhizoma extract in ameliorating trastuzumab-induced cardiotoxicity.METHODS:Homogeneous design and in vitro bioactivity assay for protection against myocardial cell injury were applied,combined with chemical fingerprinting for spectral correlation analysis,the pharmacodynamic components of Chuanxiong rhizoma extract in ameliorating trastuzumab-induced cardiomyocyte injury were explored.RESULTS:Homogeneous design showed that the optimal ethanol extraction process of Chuanxiong rhizoma was 75%ethanol,9 times of solvent volume,ethanol infiltration for 35 minutes and ultrasonic extraction for 30 minutes.Under homogeneous design test,extracts of samples 1 to 9 could ameliorate trastuzumab-induced myocardial cell injury,the strongest protective effect was S3(EC_(50)=0.037),and the weakest was S2(EC_(50)=0.317).Results of correlation analysis showed that tetramethylpyrazine,tetramethylpyrolactone I,ferulic acid and n-butylphthalide were correlated,and tetramethylpyrazine had the strongest correlation(r=0.68,P<0.05).Validation experiments showed that ligustrazine had the strongest activity,followed by ferulic acid,n-butylphthalide and ligustractone I.The results were in agreement with the spectral correlation analysis.CONCLUSIONS:The alcohol exvtraction method can affect the content of Chuanxiong rhizoma extract in ameliorating trastuzumab-induced myocardial cell injury.Ligustrazine,ligustractone I,ferulic acid and n-butylphthalide are the main active components of Chuanxiong rhizoma extract in improving trastuzumab-induced myocardial cell injury.This study may provide a scientific basis for the quality control method of traditional Chinese medicine to improve cardiotoxicity associated with anticancer drugs.

关 键 词：乳腺癌 曲妥珠单抗 心肌细胞损伤 川芎提取物 谱效相关分析 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]