王继雪 袁星星 于文慧 吕勃川 赵钢

摘要 目的：分析当归活血汤治疗下肢动脉硬化闭塞症的有效活性成分及靶点的药理作用。方法：通过中药系统药理数据库与分析平台（TCMSP）筛选当归活血汤有效活性成分及靶点，运用GeneCard及OMIM数据库获取下肢动脉硬化閉塞症（ASO）相关蛋白;通过String平台对药物-疾病靶蛋白进行蛋白质-蛋白质相互作用（PPI）网络构建，利用DAVID数据库，将所得到的当归活血汤-下肢ASO靶点进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。结果：当归活血汤药物有效活性成分234个，当归活血汤-下肢ASO作用靶点共26个;PPI网络分析结果发现IL-6、VEGFA、MMP-9、IL-10等可能是当归活血汤治疗ASO的关键靶点。共获得46条GO生物过程和167条相关信号通路，其中HIF-1、AGE-RAGE、IL-17、TNF等信号通路与下肢ASO的治疗密切相关。结论：基于网络药理学探究当归活血汤主要成分的靶点网络及其治疗下肢ASO的作用机制，为进一步对本病的基础实验研究提供新思路及科学依据。

关键词 当归活血汤;下肢动脉硬化闭塞症;靶点;作用机制;网络药理学

Mechanism of Danggui Huoxue Decoction in the Treatment of Arteriosclerosis Obliterans of the Lower Extremities Based on Network Pharmacology

WANG Jixue1，YUAN Xingxing1，2，YU Wenhui3，LYU Bochuan3，ZHAO Gang3

（1 Heilongjiang University of Traditional Chinese Medicine，Harbin 150040，China; 2 Heilongjiang Academy of Traditional Chinese Medicine，Harbin 150006，China; 3 Department of Peripheral Vascular Diseases，the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine，Harbin 150040，China）

Abstract Objective：To analyze the active components of Danggui Huoxue Decoction in the treatment of arteriosclerosis obliterans（ASO） of the lower extremities and the pharmacological effect of its target.Methods：By TCMSP database，we screened the effective active ingredients and targets of Danggui Huoxue Decoction and we used GeneCard and OMIM database to obtain lower limb ASO-related proteins; we used String platform to construct PPI network for drug-disease target proteins，and used DAVID database to obtain Danggui Huoxue Decoction-lower ASO target for GO function and KEGG pathway enrichment analysis.Results：Danggui Huoxue Decoction had 234 active ingredients，and Danggui Huoxue Decoction-lower limb ASO had 26 targets; In PPI interaction network analysis it was found that IL-6，VEGFA，MMP-9，IL-10，etc.may be the treatment of Danggui Huoxue Decoction for the key target of ASO.A total of 46 GO biological processes and 167 related signal pathways were obtained，of which HIF-1，AGE-RAGE，IL-17，TNF and other signal pathways were closely related to the treatment of lower extremity ASO.Conclusion：Based on network pharmacology，the target network of the main components of Danggui Huoxue Decoction and its mechanism of action in the treatment of lower limb ASO are explored，which provides new ideas and scientific basis for further basic experimental research on this disease.

Keywords Dangguihuoxue Decoction; Lower extremity arteriosclerosis obliterans; Target; Mechanism of action; Network pharmacology

中图分类号：R211;R289.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.23.010

下肢动脉硬化闭塞症（Arteriosclerosis Obliterans，ASO）是外周血管疾病中最常见的一种因动脉硬化斑块所致的下肢动脉闭塞性疾病。间歇性跛行是临床早期出现的典型症状，随着病情加重逐渐发展为静息痛、严重者局部缺血部位出现大范围皮肤溃烂[1]。随着经济水平的不断增长，生命质量的不断提高，人口老龄化现象日益加剧，下肢ASO的发病率呈现逐年上升的趋势[2]。……