丹参与红花配伍机制的系统生物学分析

Systems Biology Analysis of Synergistic Mechanisms Between Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos

摘要:

目的: 应用系统生物学方法模拟分析丹红注射液中丹参与红花配伍的分子机制。方法: 采用TCMGeneDIT和Agilent literature search(ALS)结合搜索方式,挖掘丹参、红花各自作用的蛋白,在BIND,BioGRID等数据库中查询蛋白间关联,分别构建丹参、红花及丹红注射液蛋白相互作用网络,应用Merge程序中的difference和intersection功能比较网络间异同。结果: 采用intersection分析得丹参和红花共有的高连接区蛋白网络含934个蛋白,经clusterONE方法提取出P<0.05的高连接区蛋白子网络4个,BiNGO插件的基因本位论聚类分析表明,其主要与RNA代谢,核因子kappa B(nuclear factor kappa B,NF-κB)级联反应,脂质代谢,Rho蛋白及小GTP酶调节4类生物学途径相关。将丹红注射液蛋白相互作用网络与丹参、红花共有高连接区蛋白网络进行difference分析,得由1 431个蛋白构成的差异网络,其主要影响细胞增殖、迁移和自噬等。结论: 本研究采用系统生物学方法模拟丹参和红花的配伍机制,其可能主要在RNA代谢,NF-κB级联反应以及细胞增殖、迁移和自噬等生物学途径上协同发挥防治疾病的作用。

Abstract:

Objective: To simulate and explore the synergistic mechanisms between Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos of Danhong injection using computer systems biology approach. Method: The combined TCMGeneDIT database and Agilent literature search (ALS) system was used to dig the protein information of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. The protein interaction networks were respectively built based on the protein-protein interaction extracted from the BIND, BioGRID database. The differences and similarities of the networks were compared via difference and intersection module of the Merge programme. Result: There were 934 proteins contained in the common highly-connected protein network of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. Four subnetworks were extracted from the common highly-connected protein network with significant difference (P<0.05) using clusterONE. Gene ontology cluster analysis demonstrated the functions of common highly-connected protein network were associated with 4 biological processes, including RNA metabolic process, nuclear factor kappa B(NF-κB) cascade, lipid homeostasis, Rho protein, Rho protein and small GTPase mediated signal transduction. The 1 431 difference protein networks extracted from the difference module analysis between Danhong injection protein and common highly-connected protein network had the relationship with the cell proliferation, migration and autophagy. Conclusion: The computer system biology approach simulated and explored the synergistic mechanisms between Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos of Danhong injection. The mechanisms might be related to the RNA metabolic process, NF-κB cascade, cell proliferation, migration and autophagy.