基于系统生物网络研究固本通络方治疗IgA肾病的分子机制

Molecular mechanism of Guben Tongluo Decoction in treating IgA nephropathy depending on a systemic biology network

目的:应用系统生物学方法研究固本通络方治疗IgA肾病的分子机制。方法:从中药分子靶标数据库中获取固本通络方潜在的药靶信息,与OMIM和IPA数据库中已知IgA肾病致病基因进行比较及功能富集分析,并构建分子调控网络。结果:固本通络方有3 851个相关蛋白,IgA肾病有25个相关蛋白,有16个蛋白为二者共有;有6个组分(黄芪、丹参、桃仁、女贞子、白茅根、鬼箭羽)作用于这16个二者共有的相关蛋白,黄芪位于该作用网络的中心;主要作用途径是影响肾素-血管紧张素系统和B细胞分泌IgA。另外,未被固本通络方覆盖的9个IgA肾病相关蛋白在细胞周期调控等生物过程中亦发挥重要作用。结论:固本通络方治疗IgA肾病可能与影响肾素-血管紧张素系统和B细胞分泌IgA有关。

Objective: To study molecular mechanism of Guben Tongluo Decoction(GBTL) in treating IgA nephropathy(IgAN) depending on a systemic biology network approach. Methods: Known IgAN associated protein annotated in OMIM and IPA database were compared with potential targets of nine ingredients in GBTL obtained from TCMID database, then performed functional enrichment analysis and constructed molecular regulation network. Results: From 25 IgAN-associated proteins, 16 were simultaneously seen in 3 851 potential targets of GBTL. Moreover, 6 out of 9 ingredients(Astragalus, Salvia miltiorrhiza, Peach kernel, Glossy privet fruit, Lalang grass rhizome, Euonymus alatus) in GBTL acted on the 16 common proteins, with Astragalus in a central position of the regulation network. The actions of 6 ingredients focused on the Renin-Angiotensin system and IgA secreted by B cell. Additionally, the remaining 9 proteins relevant to IgAN played key roles in the regulation of biological process like cell cycle. Conclusion: The mechanism underlying GBTL Decoction treating IgA nephropathy may be associated with the regulation of Renin-Angiotensin system and IgA secreted by B cell.