基于“效应成分/生物标志物-药效活性物质表达”皮尔逊分析探讨天麻钩藤药对的抗偏头痛物质基础及作用机制

Migraine is defined as one of the four diseases that most easily lead to disability which decreases the life quality seriously by WHO. Scholars start to find the effective medicines from TCM and their compound composed due to the limitation of western medicine. Tianma Gouteng Drug Pair originated from the classical Traditional Chinese Medicine prescriptions in New Treatment of Miscellaneous Diseases Syndrome. Good curative effects were produced by using the TGDP composing prescriptions in treating various migraines.The pharmacodynamics has been primarily confirmed in our research. Our research projects' group summarized that the existing research is mainly discussed the clinical efficacy and pharmacodynamics of TGDP. The rationality of compatibility of TGDP has not yet investigate from “effective components-biomarker-expression of the active substances” and the relationships between them. Base on the preliminary studies on Tianma and Gouteng chemical composition and metabolism and Pharmacodynamics, UHPLC-Q-TOF-MS, RIA,PCR, Metabolomics and Pearson correlation coefficient technology are used in the topic to elucidate the association between effect substances, biomarker, expression of the active substances in vivo, and finally reveal the scientific connotation of TGDP compatibility.

偏头痛严重影响生活质量，被WHO定为最致残的4种慢性疾病之一。由于化学药物治疗偏头痛有一定的局限性，学者开始从中药及复方中寻找有效的药物。天麻钩藤药对源于《杂病证治新义》中的天麻钩藤饮，为中医经典药对。近年来，临床运用天麻钩藤药对为核心的组方治疗各种类型的偏头痛取得良好疗效，本课题组研究已初步证实天麻钩藤药对对偏头痛的效果。但是，现有天麻钩藤药对的研究仅从临床验证分析、体内外药效学等角度开展，未从效应成分、生物标志物及其与偏头痛相关药效活性物质表达之间的关联性角度揭示其物质基础及作用机制。本课题拟在前期化学、药效及代谢等基础上，综合UHPLC-Q-TOF-MS、放射免疫（RIA）、荧光定量（PCR）、代谢组学（Metabolomics）等技术并结合统计学皮尔逊相关分析等手段，阐明天麻钩藤药对效应成分、生物标志物及其与体内偏头痛活性物质的关联性，揭示天麻钩藤药对抗偏头痛的物质基础及作用机制。

在前期天麻钩藤的化学成分、药效及体内代谢研究的基础上，本课题组综合利用UHPLC-Q-TOF-MS技术、放射免疫技术（RIA）、荧光定量技术（PCR）、代谢组学技术（Metabolomics）并充分结合统计学相关性皮尔逊分析（Pearson）等手段，通过入血成分分析得到了具体的效应成分，共计35个成分（其中原型成分20个，次生代谢成分15个）并发现了23个偏头痛相关生物标志物，初步阐明了天麻钩藤药对配伍的效应成分、生物标志物。此外，巴利森苷A和异钩藤碱（PI）分别是从天麻和钩藤中提取出来的活性单体成分，课题组前期研究证明，两者均为天麻钩藤药材中的主要入血成分，我们的研究中发现，该成分不够稳定，分别易转化为天麻素和钩藤碱，但在联合给药在动物模型大鼠中均显示具有药理活性作用。从ADME（药物进入体内后的过程）和脂质组学（药物影响内源性成分的变化）两方面内容研究了天麻钩藤组分中药对偏头痛模型大鼠的作用，将肠道菌、大鼠慢性偏头痛模型及天麻钩藤药对治疗的差异代谢物等角度进行了相关分析，对肠道菌—差异代谢物之间的联系进行了探索，从新的角度阐释了大鼠慢性偏头痛模型的发病机制及天麻钩藤药对的药效机制。.本研究共发表实验性论文4篇，其中SCI收录3篇，从更深层次揭示了天麻钩藤药对配伍的科学内涵，进而为药对配伍理论的科学性、有效性提供了数据支撑，为天麻钩藤相关的新药研发奠定了基础。