基于系统生物学对气滞胃痛颗粒药效组分解析及作用机制研究

Qizhiweitong granules were prepared by professor Wang Yongyan,who is an academician of China National Engineering Resarch Institute and a famous Chinese medicine expert.The drug is an state-level protected specie produced by Liaoning Benxi three Medicine Company Limited,after years of clinical practice,it has become the first-line clinical medication to cure epigastric pain.But the material basis of its efficacy and the mechanism of action are still not clear..Qizhiweitong granules were taken as the object of our study. Based on the preliminary study,we are going to set out from the whole compound recipe, to exosyndrome the anti-inflammatory analgesic,anti-ulcer and promoting gastrointestinal motility effective components,to identify the material basis of its efficacy,to carry out the study of synergism among each components,to launch quantitative analysis on the components by full time multi-wavelength fusion technology, based on the multi-wavelength fusion spectrum combined with pharmacodynamics experiment in vivo,to develop the study between spectrum and effect and identify the relationship between them,to carry out the study of PK-PD and determin the material basis in another way, using genomics,proteomics,metabolomics and other systems biology methods to reveal the mechanism of action in a systemic level.This topic will lay the foundation for revealing the scientific connotation of compound prescription,enhancing scientific and technological level,and promoting the development of modernization and internationalization of Chinese medicine.

气滞胃痛颗粒是由国家工程院院士、全国著名中医专家王永炎教授精心研制，辽宁本溪三药有限公司独家生产的国家级保护品种，经多年临床实践，已成为治疗胃脘痛临床一线用药。但目前其发挥药效的物质基础与作用机理尚不明确。.本课题以气滞胃痛颗粒为研究对象，从中药复方整体出发，在前期研究工作基础上，对其抗炎镇痛、抗溃疡、促胃肠动力作用有效组分组成进行表征，明确其发挥药效的物质基础；开展各组分之间的协同关系研究；采用全时段多波长融合技术对表征出的化合物进行多指标成分定量分析；以多指标成分定量分析图谱为基础，结合体内药效学实验，开展谱效关系研究，明确组分与药效间关系；开展PK-PD研究，从另一层面揭示药效基础；采用基因组学、蛋白质组学及代谢组学等系统生物学研究方法，揭示气滞胃痛颗粒复方及组分发挥药效的作用机制。该课题为解析复方科学内涵、提高科技含量、推动中药现代化与国际化发展奠定基础。

据统计，我国胃病发病率大约为7%～10%，发病人数约为3亿人左右，居世界之首。目前西药治胃病起效较快，但存在较强的毒副作用，长期服用会对身体其它器官产生危害，而中药虽疗程长，但能标本兼治，从整体出发多种途径综合治疗胃病，因此广大的胃病患者越来越倾向于取之天然的中成药制剂。气滞胃痛颗粒是由国家工程院院士、全国著名中医专家王永炎教授精心研制，辽宁本溪三药有限公司独家生产的国家级保护品种，经多年临床实践，已成为治疗胃脘痛临床一线用药。.本项目从气滞胃痛颗粒复方治疗胃脘疼痛整体研究出发，对引起胃脘疼痛的诱因进行归纳，开展药效组分解析及作用机制研究。课题组从中药复方整体出发，采用“整体-组分-成分-整体”的研究思路，对其发挥疗效的组分进行解析，已完成柴胡、延胡索等六味中药材中柴胡皂苷、延胡索生物碱等8类药效组分60余种化学成分的结构表征，基本弄清了气滞胃痛颗粒抗炎镇痛、抗溃疡、促胃肠动力药效物质组成；同时，课题组采用自主研发的全时段多波长融合指纹图谱技术，对复方中白芍药苷等成分进行多指标成分定量分析研究，完成了气滞胃痛颗粒复方含量测定方法的建立，为全面控制气滞胃痛颗粒复方质量提供了一种新方法；最后，课题组采用代谢组学的研究方法，结合现有的药理学评价指标，系统研究气滞胃痛颗粒复方作用于发挥抗炎镇痛、抗溃疡、促胃肠动力三大目标评价模型后的生物应答信息，寻找潜在的生物标记物，确定药物发挥药效的作用途径。在抗炎镇痛药效作用研究中，已鉴定Niacinamide等8个炎症小鼠体内发生显著变化的代谢物小分子，调控丙戊酸代谢，皮质酮代谢等4条代谢通路；在抗溃疡药效作用研究中，已鉴定出找Sphingosine-1-phosphate、Stearic acid等13个内源性物质分别作用于氨基酸代谢、鞘氨醇代谢等5条信号通路；在促胃肠动力药效作用研究中，共鉴定出N1，N12-Diacetylspermine等9个生物标记物作用于Beta-alanine信号通路；该项目已发表论文4篇，其中SCI论文1篇（影响因子3.73），申请专利1项，获授权专利1项。该项目的研究成果提高了气滞胃痛颗粒产品质量，促进了该产品的市场竞争力，全面提升产品的技术含量，为企业赢得了可观的经济效益及社会效益。