回顾性“真实世界”研究原发性失眠中医证治规律及高频中药的作用机制

Retrospective real world study on the rules of traditional Chinese medicine syndrome treatment and the mechanism of high-frequency herbs in primary insomnia

目的:探讨原发性失眠中医证治规律及高频中药甘草、酸枣仁、远志、首乌藤、柏子仁"养心安神"的作用机制。方法:回顾性分析172例就诊于河南中医药大学第一附属医院、临床第一诊断为原发性失眠的患者数据,运用Python、E-Charts、SPSS软件总结其证治规律,借助网络药理学和分子对接方法分析高频中药发挥作用的潜在机制。结果:纳入172例患者病历资料,涵盖中医证型32种,提取病位证素6个,病性证素10个,涉及中药212味,常用中药(频次≥20)聚类分析可分为6类;通过TCMSP、GeneCards、OMIM、Disgenet等数据库筛选频数排名前5位的高频中药甘草、酸枣仁、远志、首乌藤、柏子仁有效活性成分94个,作用靶点448个;疾病靶点1433个,其中包括通过GEO数据库GSE98566芯片筛选的差异基因119个;获得高频中药与疾病交集靶点85个;PPI网络主要涉及AKT1、TP53、MYC、STAT3、ESR1等关键靶蛋白;KEGG富集得到20条通路;分子对接提示甘草异黄酮与MYC蛋白结合情况最佳。结论:中医药辨治原发性失眠有规律可循,且遵循"以心为本,兼顾肝脾;以顺为治,养心安神;以平为期,补虚泻实"为宗旨,高频中药发挥"养心安神"作用具有多组分、多靶点、多途径等特点。

OBJECTIVE To explore the rules of syndrome and treatment of primary insomnia and the mechanism of "nourishing the heard and tranquilize the mind" of high-frequency herbs such as Liquorice Root, Jujube Seed, Radix Polygalae, Radix Polygoni and Semen Platycladi.METHODS Based on the real world study, the clinical data of 172 patients with primary insomnia in the First Affiliated Hospital of Henan University of Chinese Medicine were retrospectively analyzed. Python, E-Charts and SPSS softwares were used to summarize the rules of syndrome and treatment, and the potential action mechanism of high-frequency herbs was analyzed by network pharmacology and molecular docking.RESULTS The 172 patients with primary insomnia included 32 TCM syndromes, 6 disease site syndromes element and 10 disease syndromes element involving 212 herbs. Cluster analysis on commonly used herbs(frequency≥20) could be divided into 6 categories. Through TCMSP, GeneCards, OMIM, Disgenet and other databases, 94 active ingredients were screened out, 448 action targets and 1 433 disease targets were identified including 119 differential genes between healthy people and insomnia patients screened by GEO database GSE98566 chip. There were 85 intersection targets of high frequency herbs and insomnia. PPI network mainly involved key target proteins such as AKT1, TP53, MYC, STAT3 and ESR1. Totally 20 pathways were obtained by KEGG enrichment. Molecular docking indicated that Licoagroisoflavone had the best combination with MYC protein.CONCLUSION The treatment rules of primary insomnia follow the principle of "take heart as fundamental, give consideration to liver and spleen, follow the pathogenesis of the disease to use sedative herbs, balance sickness deficiency and surplus" as the rule. High-frequency herbs play a role in "nourishing the heard and tranquilize the mind", which have the characteristics of multi-component, multi-target and multi-pathway.