当归治疗慢性咳嗽的中医处方规律及其分子机制研究

Study on Traditional Chinese Medicine Prescription Rules and Molecular Mechanism of Angelicae Sinensis Radix in the Treatment of Chronic Cough

关键词:  当归  慢性咳嗽  用药规律  网络药理  阿魏酸  磷脂酰肌醇3-激酶受体1

Key words:  Angelicae Sinensis Radix  chronic cough  rule of medication  network pharmacology  ferulic acid  phosphatidylinositol 3-kinase receptor 1

摘要:

目的 在“主咳逆上气”中医药理论的指导下，探究当归治疗慢性咳嗽的中医临床处方规律及其分子机制研究。方法 检索相关数据库收集临床上治疗慢性咳嗽的当归复方，对当归复方所含中药的频次、性味归经、四气五味及其功效进行统计分析，并对频数较高的中药进行系统聚类分析。利用TCMSP等数据库筛选当归所含成分及其靶点、慢性咳嗽疾病靶点以及当归治疗慢性咳嗽的交集靶点，对交集靶点进行蛋白质-蛋白质互作网络及KEGG通路分析，构建成分-靶点-通路网络；将拓扑分析所得关键成分与靶点进行分子对接验证，同时通过动物实验验证关键成分阿魏酸镇咳对磷脂酰肌醇3-激酶受体1(phosphatidylinositol 3-kinase receptor 1，PIK3R1)的影响。结果 收集治疗慢性咳嗽的当归复方423首，涵盖419味中药，其中以补虚药、化痰止咳平喘药多见，以归肺、脾、肝经居多，以性温、寒、平，味甘、苦、辛为主；检索获得当归活性成分41个，当归治疗慢性咳嗽的靶点157个，通路164条；当归关键成分与关键靶点分子对接中有较好的结合活性，当归关键成分阿魏酸能明显延长小鼠咳嗽潜伏期，减少咳嗽次数，降低肺组织PIK3R1及其基因的表达水平。结论 临床上当归经常配伍成复方用于治疗慢性咳嗽，其通过作用于多成分、多靶点而发挥治疗作用，当归所含阿魏酸通过抑制PIK3R1而发挥镇咳作用。

Abstract:

OBJECTIVE To explore the Chinese medicine clinical prescription rules and molecular mechanism of Angelicae Sinensis Radix for chronic cough under the guidance of the traditional Chinese medicine theory of "Treating Cough and Reversing Upper Qi". METHODS Relevant databases were searched to collect Angelicae Sinensis Radix prescription for the clinical treatment of chronic cough. Statistical analysis was carried out on the frequency, nature and flavour and meridian tropism, four properties and five flavors and their efficacy of Angelicae Sinensis Radix prescriptions. And the traditional Chinese medicine of high frequency was analyzed systematically by cluster analysis. Use TCMSP and other databases to screen the components and targets contained in Angelicae Sinensis Radix, the targets of chronic cough disease and the intersection targets of Angelicae Sinensis Radix in the treatment of chronic cough. The intersection targets were used to analyze the protein-protein interaction network and KEGG pathway and construct components-targets-pathway networks. Using molecular docking to verify the blinding activity between the key components and targets obtained by topological analysis, animal experiments were done to verify cough suppression of ferulic acid based on phosphatidylinositol 3-kinase receptor 1(PIK3R1). RESULTS Four hundred and twenty-three Angelicae Sinensis Radix prescriptions for the treatment of chronic cough were collected, covering 419 traditional Chinese medicines, of which the most common were tonic, phlegm-relieving, cough-relieving and asthma-relieving drugs, most of which were related to the lung, spleen, and liver meridians, and mainly warm, cold, flat, sweet, bitter and acrid; the search obtained 41 active ingredients of Angelicae Sinensis Radix, 157 targets and 164 pathways of Angelicae Sinensis Radix in the treatment of chronic cough. The key components of Angelicae Sinensis Radix had good binding activity in the molecular docking of key targets, and the key component of Angelicae Sinensis Radix ferulic acid could significantly prolong the cough latency of mice, reduce the number of coughs and reduce the expression levels of PIK3R1 and its genes in lung tissue. CONCLUSION In clinical practice, Angelicae Sinensis Radix is often combined into compound prescriptions for the treatment of chronic cough. It exerts a therapeutic effect by acting on multiple components and multiple targets. The ferulic acid contained in Angelicae Sinensis Radix exerts an antitussive effect by inhibiting PIK3R1.