基于网络药理学及分子对接探讨猪胶原血管紧张素转换酶抑制肽的降压机制  

Antihypertensive mechanism of porcine collagen ACE inhibitory peptides based on network pharmacology and molecular docking

作　　者：周法婷 李迪 李开凤 蒋忠桂 魏蝶 丛之慧 陈井生 顾欣 肖国生 ZHOU Fating;LI Di;LI Kaifeng;JIANG Zhonggui;WEI Die;CONG Zhihui;CHEN Jingsheng;GU Xin;XIAO Guosheng(College of Biological and Food Engineering,Chongqing Three Gorges University,Chongqing 404100,China)

机构地区：[1]重庆三峡学院生物与食品工程学院,重庆404100

出　　处：《食品与发酵工业》2024年第18期217-224,共8页Food and Fermentation Industries

基　　金：重庆市技术创新与应用发展专项重点项目(cstc2021jscx-tpyzxX0004);重庆市万州区生猪产业链全程绿色生产技术创新创业团队项目;研究生科研创新项目(YJSKY23024)。

摘　　要：该文通过网络药理学及分子对接研究了猪胶原蛋白源血管紧张素转换酶(angiotensin converting enzyme,ACE)抑制肽改善高血压的作用机制。使用生物信息学工具,分析和预测生物活性肽的性质;利用数据库平台筛选出RL(Arg-Leu)的潜在靶点和改善高血压的相关靶点,将两者取交集获得活性肽RL改善高血压的潜在靶点;构建共同靶点间的蛋白互作网络,并对共同靶点进行基因本体论(gene ontology,GO)功能注释和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;通过分子对接,研究目标肽与高血压关键靶点的结合机制。结果表明,硅法筛选出的猪胶原蛋白活性肽RL可通过调节多种生物学过程在不同的细胞成分中发挥多种分子功能,通过PI3K-Akt信号通路、白细胞介素-17信号通路、T细胞受体信号通路、MAPK信号通路、Wnt信号通路以及血小板活化通路等发挥降血压的作用,与关键靶点ACE(6p0z)的相互作用最稳定,通过氢键与靶点蛋白结合,主要与Asp-153、Gln-150、Glu-143等多种氨基酸残基结合,从而影响靶点在各个通路中的作用,是辅助治疗高血压的最佳核心靶点。This article investigated the mechanism of angiotensin converting enzyme(ACE)inhibitory peptides derived from porcine collagen in improving hypertension through network pharmacology and molecular docking.Bioinformatics tools were used to analyze and predict the properties of hypotensive peptides from porcine collagen sources.The potential targets of RL(Arg-Leu)and related targets of improving hypertension were screened by the database platform,and the potential targets of improving hypertension by active peptide RL were obtained by intersecting the two.The protein interaction network between common targets was constructed,and the common targets were annotated by the gene ontology(GO)function and enriched by the kyoto encyclopedia of genes and genomes(KEGG)pathway.Through molecular docking,the binding mechanism of the target peptide to the key target of hypertension was studied.Results showed that porcine collagen active peptide RL screened by the silicon method could play a variety of molecular functions in different cell components by regulating various biological processes.It played a role in lowering blood pressure through the PI3K-Akt signaling pathway,interleukin-17(IL-17)signaling pathway,T cell receptor signaling pathway,MAPK signaling pathway,Wnt signaling pathway,and platelet activation pathway.It interacted with the key target ACE(6p0z)most statically and bound to the target protein through hydrogen bonding.It was mainly combined with various amino acid residues such as Asp-153,Gln-150,Glu-143,and so on,thus affecting the role of the target in each pathway,and was the best core target for the treatment of hypertension.

关 键 词：猪胶原蛋白 生物活性肽 高血压 网络药理学 分子对接 

分 类 号：TS251.9[轻工技术与工程—农产品加工及贮藏工程]