基于网络药理学及体外实验方法探究瓜蒌对低氧诱导的大鼠肺动脉平滑肌细胞增殖、迁移的影响  

Exploration of the effects of Trichosanthes kirilowii Maxim.on the hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells based on network pharmacology and in vitro experiments

作　　者：黄攀 王玉香 马兰[1] HUANG Pan;WANG Yuxiang;MA Lan(Qinghai University,Xining 810016,China)

机构地区：[1]青海大学,西宁810016

出　　处：《中国高原医学与生物学杂志》2024年第4期217-227,共11页Journal of Chinese High Altitude Medicine & Biology

基　　金：国家自然科学基金项目(32060207);青海省自然科学基金项目(2021-ZJ-738);2022年青海省“昆仑英才·高端创新创业人才”计划项目。

摘　　要：目的运用网络药理学和体外实验方法探究瓜蒌对低氧诱导的大鼠肺动脉平滑肌细胞增殖、迁移的影响。方法利用TCMSP、Pubchen、Swiss Target Prediction、GeneCards、OMIM、DisGeNET、STRING、PDB等数据库预测瓜蒌作用于低氧性肺动脉高压的潜在靶点基因,筛选出核心靶点基因后进行富集分析,采用分子对接技术验证网络药理学预测结果,通过体外实验观测瓜蒌提取物对低氧诱导的大鼠肺动脉平滑肌细胞增殖、迁移的影响。结果通过综合多个数据库得到210个瓜蒌抗低氧性肺动脉高压潜在靶点基因,进一步筛选得到IL6、ESR1、AKT1、BCL2等43个核心靶点基因。GO、KEGG富集分析结果表明,瓜蒌通过影响PI3K/AKT和FoxO、Ras等信号通路发挥抗低氧性肺动脉高压作用。在分子对接实验中,瓜蒌中的多种成分与多种靶点基因有着良好的结合能力。通过体外实验发现,瓜蒌提取物可以抑制低氧诱导的大鼠肺动脉平滑肌细胞的增殖、迁移。结论瓜蒌提取物可以通过多成分、多靶点、多通路抑制低氧诱导的大鼠肺动脉平滑肌细胞的增殖、迁移,进而对低氧性肺动脉高压发挥保护作用。Objective To investigate the effects of Trichosanthes kirilowii Maxim.on the hypoxia-induced proliferation and migration of rat pulmonary artery smooth muscle cells(PASMCs)by adopting network pharmacology and in vitro experiments.Methods Various databases,including TCMSP,Pubchen,Swiss Target Prediction,Gene-Cards,OMIM,DisGeNET,STRING,PDB,were utilized to predict potential target genes of Trichosanthes kirilowii Maxim.in hypoxic pulmonary hypertension.Core target genes were identified for enrichment analysis.Molecular docking technology was utilized to confirm the prediction results of network pharmacology.In vitro experiments were carried out to evaluate the effects of Trichosanthes kirilowii Maxim.extract on the hypoxia-induced proliferation and migration of rat PASMCs.Results A total of 210 potential target genes of Trichosanthes kirilowii Maxim.against hypoxic pulmonary hypertension were identified after integrating multiple databases.Further screening revealed 43 core target genes,including IL6,ESR1,AKT1 and BCL2.The results of CO and KEGG enrichment analyses indicated that Trichosanthes kirilowi Maxim.exerted its anti-hypoxic pulmonary hypertension effects by modulating PI3K/AKT,FoxO,Ras and other signaling pathways.Molecular docking demonstrated that various components in Trichosanthes kirilowii Maxim.exhibit strong binding abilities with different target genes.In vitro experiments revealed that the extract of Trichosanthes kirilowi Maxim.effectively inhibits the hypoxia-induced proliferation and migration of rat PASMCs.Conclusion The extract of Trichosanthes kirilowi Maxim.may inhibit the hypoxia-induced proliferation and migration of rat pulmonary artery smooth muscle cells through multiple components,multiple targets and multiple pathways,thereby exerting a protective effect on hypoxic pulmonary arterial hypertension.

关 键 词：网络药理学 瓜蒌 低氧 大鼠 平滑肌 细胞 增殖 迁移 

分 类 号：R393[医药卫生—基础医学]