基于成分表征和网络药理学研究黄芪丹参煎液治疗急性肾损伤的质量标志物  

Study on the Q-Markers for Huangqi-Danshen Decoction in the Treatment of Acute Kidney Injury Based on Constituents Characterization and Network Pharmacology

作　　者：陈剑平[1,2] 李常慧[1] 黄诗莹 陈秋谷 王蕤 卢锦华 刘新辉 刘志承 张尚斌[1,2] Chen Jianping;Li Changhui;Huang Shiying;Chen Qiugu;Wang Rui;Lu Jinhua;Liu Xinhui;Liu Zhicheng;Zhang Shang-bin(Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Guangdong Shenzhen 518033,China;Shenzhen Key Laboratory for Hospital Chinese Medicine Preparation,Shenzhen Traditional Chinese Medicine Hospital;Shenzhen Nanyue Pharmaceutical Co.Ltd.)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院、深圳市医院中药制剂研究重点实验室 [3]深圳南粤药业有限公司

出　　处：《中国药师》2022年第12期2079-2086,共8页China Pharmacist

基　　金：深圳市科技计划项目(编号:JSGG20191129102216637、ZDSYS20160608151545865);深圳市医疗卫生三名工程项目(编号:SZZYSM202111002)。

摘　　要：目的:基于超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS)和网络药理学研究黄芪丹参煎液治疗急性肾损伤的质量标志物(Q-Marker)。方法:采用UPLC-Q-TOF-MS/MS技术,对黄芪丹参煎液的化学成分进行表征;运用SwissTargetPrediction等数据库预测黄芪丹参煎液化学成分与急性肾损伤的靶点和通路,绘制出“中药-核心成分-关键靶点-通路-疾病”网络图,预测与药效相关性最大的核心化合物指标;通过分子对接进一步验证所筛选的潜在Q-Marker。结果:从黄芪丹参煎液中共鉴定出20个化学成分;通过网络药理学筛选得到黄芪丹参煎液中与急性肾损伤相关的129个靶点,京都基因和基因组百科全书(KEGG)分析表明其主要从磷脂酰肌醇激酶-丝氨酸/苏氨酸蛋白激酶(PI3K-Akt)等信号通路实现对急性肾损伤的治疗,提示咖啡酸、黄芪甲苷、丹参醇A、黄芪皂苷Ⅱ和迷迭香酸等5个核心成分为黄芪丹参煎液治疗急性肾损伤的潜在Q-Marker。分子对接结果提示网络药理预测的Q-Marker可靠性较高。结论:通过成分表征和网络药理学关联分析,预测黄芪丹参煎液治疗急性肾损伤的潜在Q-Marker,为其整体质量控制提供参考依据。Objective: To analyze the quality markers(Q-Markers) of Huangqi Danshen decoction in the treatment of acute kidney injury based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and network pharmacology. Methods: The chemical constituents of Huangqi Danshen decoction were analyzed by UPLC-Q-TOF-MS/MS. SwissTargetPrediction and other databases were used to predict the targets and pathways of chemical constituents and acute kidney injury, and the “traditional Chinese medicine-core component-key target-significant pathway-disease” connection network was drawn to predict the core compound index with the greatest pharmacological correlation. The screened potential Q-Markers were further validated by molecular docking.Results: A total of 20 components were identified from Huangqi Danshen decoction. Through network pharmacological technology, 129 targets of Huangqi Danshen decoction related to acute kidney injury were screened. KEGG analysis showed that acute kidney injury was mainly treated by PI3 K-Akt signaling pathway, etc. It was suggested that caffeic acid, astragaloside IV, danshenol A, astragaloside II and rosmarinic acid may be the potential Q-Markers of Huangqi Danshen decoction in the treatment of acute kidney injury. Molecular docking results showed that the Q-Markers of network pharmacology prediction were of high reliability.Conclusion: Through constituents characterization and network pharmacological association analysis, the potential Q-Markers of Huangqi Danshen decoction in the treatment of acute kidney injury are predicted, which can provide basis for its overall quality control.

关 键 词：黄芪 丹参 急性肾损伤 质量标志物 网络药理学 超高效液相色谱-四极杆飞行时间串联质谱 

分 类 号：TQ460.72[医药卫生—药物分析学]