摘要
背景壮腰通络方是临床治疗腰椎间盘退行性病变(LIDD)的有效方剂,但该方化学成分及具体作用机制尚不明确。目的明确壮腰通络方水提液中的主要化学成分,并进一步探讨其延缓LIDD的潜在作用机制。方法2020年采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS)技术分析壮腰通络方中的化学成分,并在此基础上采用网络药理学方法,获取基于质谱分析的壮腰通络方化学成分的作用靶点。同时,通过疾病靶点数据库获得LIDD疾病靶点。采用韦恩图分析获得壮腰通络方治疗LIDD的交集靶点。通过STRING 11.0数据库获得交集靶点蛋白与蛋白互作(PPI)网络信息,并提取其网络中的核心靶点。最后,对核心靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果基于UPLC-Q-TOF-MS/MS技术获得壮腰通络方中129种化学成分。随后,将203个药物靶点与LIDD疾病靶点映射共获得96个交集靶点。PPI分析发现丝氨酸/苏氨酸蛋白激酶(AKT1)、胰岛素蛋白(INS)、白介素6(IL-6)、原癌基因蛋白(FOS)、胱天蛋白酶3(CASP3)等是核心靶点。GO富集分析确定了1022条生物过程信息、28条细胞组成信息、51条分子功能信息。KEGG通路富集分析确定了98条相关信号通路,主要包括:HIF-1 signaling pathway、JAK-STAT signaling pathway、Relaxin signaling pathway、p53 signaling pathway、MAPK signaling pathway等。结论本研究初步揭示了壮腰通络方包含的化学成分及其延缓LIDD的药效靶点、生物途径及作用机制,为深入解析其药效物质基础及作用机制提供了参考依据。
Background Zhuangyaotongluo decoction is effective for lumbar intervertebral disc degeneration(LIDD),but its chemical constituents and mechanism of action are unclear.Objective To ascertain the major chemical constituents of Zhuangyaotongluo decoction,and to explore its potential mechanism of action in delaying the progression of LIDD.Methods In 2020,Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)was used to analyze the major chemical constituents of Zhuangyaotongluo decoction,and network pharmacology with mass spectrographic analysis was used to ascertain its potential mechanism of action targets.Therapeutic targets for LIDD were collected via checking 5 therapeutic target databases,and the common ones were identified by using Venn diagram analysis.The protein-protein interaction(PPI)networks of these common targets were obtained from the STRING 11.0 database,and the core targets were extracted from them.Finally,GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for analyzing the core targets.Results Zhuangyaotongluo decoction was found to be composed of 129 chemical constituents by UPLC-Q-TOF-MS.Then 96 common targets were obtained by mapping 203 action targets of Zhuangyaotongluo decoction to therapeutic targets for LIDD.PPI network analysis found that AKT1,INS,IL-6,FOS,and CASP3 were core targets.The GO analysis identified 1022 biological process information,28 cellular components information,and 51 molecular function information.Analysis using KEGG identified 98 related signaling pathways,mainly including HIF-1 signaling pathway,JAK-STAT signaling pathway,Relaxin signaling pathway,p53 signaling pathway,and MAPK signaling pathway.Conclusion This study revealed the chemical constituents contained in Zhuangyaotongluo decoction and their action targets,biological pathways and mechanisms of action for delaying LIDD,providing a reference basis for future in-depth analysis of its therapeutic substance basis and mechanisms of action.
作者
孙凯
朱立国
魏戌
银河
李秋月
秦晓宽
杨博文
SUN Kai;ZHU Liguo;WEI Xu;YIN He;LI Qiuyue;QIN Xiaokuan;YANG Bowen(Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Beijing Key Laboratory of Traditional Chinese Bone-setting Techniques,Beijing 100700,China)
出处
《中国全科医学》
CAS
北大核心
2021年第35期4437-4446,共10页
Chinese General Practice
基金
国家自然科学基金重点资助项目(81930118)
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202003)
江西省博士后研究人员科研项目(2018RC13)
2020年度中国中医科学院博士研究生创新人才培养基金项目。
关键词
椎间盘退行性变
腰椎
壮腰通络方
药理作用分子作用机制
超高效液相色谱-四极杆飞行时间串联质谱
网络药理学
Intervertebral disc degeneration
Lumbar vertebrae
Zhuangyaotongluo decoction
Molecular mechanisms of pharmacological action
Ultra performance liquid chromatography-Q-TOF-MS/MS
Network pharmacology
