基于谱毒关系和肝毒网络整合模式的柴胡水煎液肝毒物质基础研究  

Study on basis of liver toxicity of decoction Bupleurum chinense based on integrated model of spectrum toxicity relationship and liver toxicity network

作　　者：侯磊 王亮[4] 刘闰平 孙蓉[2,3] HOU Lei;WANG Liang;LIU Run-ping;SUN Rong(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Institute of Advanced Medical Sciences,Shandong University,Jinan 250012,China;The Second Hospital of Shandong University,Jinan 250033,China;Shandong Academy of Chinese Medicine,Jinan 250014,China;Beijing University of Traditional Chinese Medicine,Beijing 100029,China)

机构地区：[1]山东中医药大学,山东济南250355 [2]山东大学高等医学研究院,山东济南250012 [3]山东大学第二医院,山东济南250033 [4]山东省中医药研究院,山东济南250014 [5]北京中医药大学,北京100029

出　　处：《中草药》2020年第10期2798-2806,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然基金面上项目(81773997);山东省重点研发计划(重大关键技术)项目(2016ZDJS07A21);山东省重点研发计划项目(2017CXGC1301);泰山学者工程专项经费资助(ts201511107)。

摘　　要：目的研究柴胡水煎液HPLC指纹图谱及体外肝毒性的谱毒关系,构建柴胡水煎液致肝毒性的作用网络,整合谱毒关系和网络毒理学预测柴胡水煎液致肝毒性的物质基础。方法采用HPLC法建立10批次柴胡水煎液的指纹图谱;测定柴胡水煎液对正常人肝细胞L02中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的含量;采用灰色关联分析法进行谱毒关联分析,初步确定肝毒性成分。结合网络毒理学,预测肝毒性候选成分。整合分析探究柴胡水煎液致肝毒性的成分。结果建立了柴胡水煎液指纹图谱,共标定29个共有峰;根据灰色关联度大小排序,13、12、8、26、10、14、27、11号共有峰与L02细胞ALT含量有较高关联度;12、13、26、8、10、14、27、11号共有峰与L02细胞AST含量有较高关联度。网络毒理学推测柴胡致肝毒性的成分为豆甾醇、黄芩苷等17个;整合分析确定柴胡致肝毒性的成分为共有峰13、12、8、26、10、14、27、11代表的成分及豆甾醇、黄芩苷、柴胡皂苷D等。结论柴胡水煎液致肝毒性是多种成分共同作用的结果,本研究可对下一步柴胡水煎液致肝毒性的物质基础研究提供数据支持。Objective To study the HPLC fingerprint of Bupleurum chinense and the relationship between the spectrum and the toxicity in vitro, construct the network of the liver toxicity induced by B. chinense, and integrate the spectrum and the network toxicology to predict the material basis of the liver toxicity induced by B. chinense. Methods The fingerprints of 10 batches of decoction of B. chinense were established by HPLC, the contents of ALT and AST in L02 cells were determined by decoction of B. chinense, and the toxic components of liver were preliminarily determined by the method of grey correlation analysis. Combined with network toxicology, the candidate components of hepatotoxicity were predicted. Integrated analysis on the components of liver toxicity induced by decoction of B. chinense. Results The established fingerprint of B. chinense was calibrated with 29 common peaks. The results of grey correlation analysis showed that common peaks 13, 12, 8, 26, 10, 14, 27 and 11 had a high correlation degree with the ALT content of L02 cells. The common peaks of 12, 13, 26, 8, 10, 14, 27 and 11 had a high correlation degree with the AST content of L02 cells. According to the network toxicology, 17 components of B. chinense, stigmasterol, baicalin, etc were speculated to be the hepatotoxicity components of B. chinense. The integrated analysis initially determined that the hepatotoxicity components of B. chinense were 13, 12, 8, 26, 10, 14, 27 and 11 peaks in total, and stigmasterol, baicalin, saikosaponin D, etc. Conclusion The hepatotoxicity of B. chinense is the result of the interaction of various components. This study can provide data support for the further research on the material basis of B. chinense hepatotoxicity.

关 键 词：柴胡 肝毒性 谱毒关系 作用网络 网络毒理学 物质基础 HPLC 指纹图谱 L02细胞 丙氨酸转氨酶 天冬氨酸转氨酶 灰色关联分析法 整合分析 豆甾醇 黄芩苷 柴胡皂苷D 

分 类 号：R285.5[医药卫生—中药学]