基于分子對接與網絡藥理學探討蘇黃止咳膠囊治療咳嗽變異性哮喘的作用機制

張恩铚 杜丹陽 劉利根 石心紅

摘要 目的：通過分子對接與網絡藥理學技術，深度發掘蘇黃止咳膠囊主要活性成分，明確其作用靶點與信號通路，分析其治療咳嗽變異性哮喘（CVA）多靶點、多通路的干預作用機制，闡明蘇黃止咳膠囊（SH）的藥效物質基礎及作用機制。方法：依托于網絡藥理學技術與分子對接技術，從SH中篩選活性化合物，并對其通路進行分析。結果：篩選得到75個活性化合物，其中麻黃與前胡所含化合物占比最多，各為16種，其余依此為紫蘇子13種、枇杷葉11種、五味子7種、牛蒡子5種、地龍4種、紫蘇葉3種。共得到CVA相關靶點429個，共得到相關通路316條，其中涉及相關疾病信號通路2條，與炎癥相關通路4條，肺損傷保護通路1條。結論：本文初步探討了SH的主要活性活性成分、相關靶點及涉及通路，預測其治療CVA的藥效物質基礎及其作用機制，為后續處方二次開發優化及臨床治療CVA的療效評價指標提供參考與物質基礎。

關鍵詞 分子對接;網絡藥理學;蘇黃止咳膠囊;咳嗽變異性哮喘;作用機制

Mechanism of Suhuang Zhike Capsules Against Cough Variant Asthma Based on Molecular Docking and Network Pharmacology

ZHANG Enzhi，DU Danyang，LIU Ligen，SHI Xinhong

（School of Traditional Chinese Pharmacy，China Pharmaceutical University，Nanjing 211198，China）

Abstract Objective：To explore the main active components of Suhuang Zhike Capsules（SH），identify the targets and signaling pathways，analyze the multi-target and multi-pathway intervention mechanism in the treatment of cough variant asthma（CVA），and clarify the pharmacodynamic material basis and mechanism of action of SH based on molecular docking method and network pharmacology.Methods：Based on the network pharmacology and molecular docking，active components of SH were screened out and the corresponding pathways were analyzed.Results：Seventy-five active components were screened out from SH，and Ephedrae Herba and Peucedani Radix contained the largest proportions of components，16 for each one，followed by Perillae Fructus for 13，Eriobotryae Folium for 11，Schisandrae Chinensis Fructus for 7，Arctii Fructus for 5，Pheretima for 4，and Perillae Folium for 3.In addition，a total of 429 targets related to CVA and 316 pathways were obtained，including two disease-related signaling pathways，four inflammation-related pathways，and one protection pathway against lung injury.Conclusion：The present study preliminarily discussed the main active components，related targets，and pathways involved in SH and predicted the pharmacodynamic material basis and mechanism of SH against CVA，which is expected to provide references and material basis for the subsequent optimization of prescription modification and research on the efficacy evaluation indexes in the clinical treatment of CVA.

Keywords Molecular docking;Network pharmacology;Suhuang Zhike Capsules; Cough variant asthma;Mechanism of action

中圖分類號：R285;R256.12文獻標識碼：Adoi：10.3969/j.issn.1673-7202.2022.10.003

咳嗽變異性哮喘（Cough Variant Asthma，CVA）是臨床上一種較為特殊的哮喘類型，是導致成人慢性咳嗽的主要病因。臨床特點主要表現為持續性或慢性咳嗽，在清晨和夜晚咳嗽尤為劇烈，冷空氣、感冒、油煙等會加重咳嗽[1]。患者無明顯臨床感染表現，亦無呼吸困難、氣促、明顯喘息等。一般認為CVA是哮喘或其亞型的前期，也將其稱之為隱匿性哮喘[2]。當前有關CVA的具體發病機制尚不明晰，西醫主要以支氣管擴張劑與吸入激素治療為主，但存在患者接受及依存性差等問題，無法堅持長期治療，病情會反復發作。……