基于网络药理学、分子对接及体外实验探讨熊氏十味温胆汤促胆固醇逆转运防治动脉粥样硬化的作用机制

doi:10.12092/j.issn.1009-2501.2025.08.003

摘要/Abstract

摘要： 目的：通过网络药理学、分子对接及体外实验研究熊氏十味温胆汤（SWD）对ABCA1表达和胆固醇转运的影响,探讨其促胆固醇逆转运（RCT）的通路机制。方法：利用TCMSP、HERB平台,筛选SWD药物有效成分,并预测RCT靶点,构建成分-靶点网络图,用STRING数据库进行蛋白-蛋白相互作用（PPI）网络构建及基因本体（GO）、京都基因与基因组百科全书（KEGG）通路富集分析;选取SWD关键活性成分用AutoDock Vina与ABCA1蛋白、miR-33进行分子对接。体外实验采用RAW264.7建立泡沫细胞模型,通过油红O染色和NBD-胆固醇,并使用慢病毒过表达细胞miRNA-33,研究SWD对RAW264.7细胞的脂质蓄积和胆固醇流出率的影响,用Western blotting检测ABCA1表达情况。结果：根据网络药理学获得SWD活性成分336个,RCT靶点267个,RCT与SWD交集靶点46个,涉及脂质与动脉粥样硬化等多条信号通路;分子对接显示核心活性成分与ABCA1、miR-33有较稳定的结合构象;体外实验发现SWD组细胞脂质含量明显降低（P<0.01）,胆固醇流出率明显增加（P<0.01）,ABCA1蛋白表达明显上调（P<0.01）,而miR-33过表达组ABCA1的表达显著下降（P<0.01）。结论：SWD具有多成分、多靶点的特点,可能通过miRNA-33-ABCA1通路促RCT防治动脉粥样硬化（AS）。

关键词: 熊氏十味温胆汤, 动脉粥样硬化, 胆固醇逆向转运, ABCA1, miR-33

Abstract: AIM: Xiongshi Shiwei Wendan decoction (SWD) comes from Xiong Jibai, a master of traditional Chinese medicine, and has been widely used in the treatment of AS. ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS. The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacology, molecular docking and in vitro experiments, and explore the pathway mechanism of promoting reverse cholesterol transport (RCT). METHODS: The active components of SWD drugs were screened by TCMSP and HERB databases, RCT targets were predicted, the component-target network map was constructed, the PPI network was constructed and the GO and KEGG pathways were enriched and analyzed by STRING database, and the key active components of SWD were selected for molecular docking with ABCA1 protein and miR-33 by AutoDockVina. In vitro, RAW264.7 was used to establish foam cell model, oil red O staining, NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells. Western blotting was used to detect the expression of ABCA1. RESULTS: According to network pharmacology, 336 active components of SWD, 267 targets of RCT and 46 targets of intersection of RCT and SWD were obtained, which involved multiple signal pathways such as lipid and atherosclerosis. Molecular docking showed that the main active components had stable conformation with ABCA1 and miR-33. In vitro experiment, it was found that the lipid content was significantly decreased (P<0.01), the cholesterol outflow rate was significantly increased (P<0.01) and the expression of ABCA1 protein was up-regulated in SWD group (P<0.01), but the expression of ABCA1 in miR-33 overexpression group was significantly decreased (P<0.01). CONCLUSION: SWD has the characteristics of multi-components and multi-targets, which can promote RCT and treat AS through miRNA-33-ABCA1 pathway.

Key words: Xiongshi Shiwei Wendan decoction, atherosclerosis, reverse cholesterol transport, ABCA1, miR-33

中图分类号:

R965.2

马星雨, 谢雪姣, 李春巧, 张正. 基于网络药理学、分子对接及体外实验探讨熊氏十味温胆汤促胆固醇逆转运防治动脉粥样硬化的作用机制[J]. 中国临床药理学与治疗学, 2025, 30(8): 1026-1036.

MA Xingyu^{1, 2}, XIE Xuejiao², LI Chunqiao¹, ZHANG Zheng¹. Study on the mechanism of Xiongshi Shiwei Wendan decoction promoting RCT and treat AS based on network pharmacology, molecular docking and in vitro experiment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1026-1036.

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