大黄附子汤治疗慢性肾衰竭的网络药理学研究及初证  

Study on the material basis and mechanism of Rhizome Aconiti Decoction in treating chronic renal failure by network pharmacology

作　　者：郝鹏飞 钟书婷[1] 张超云 黄显章 HAO Peng-fei;ZHONG Shu-ting;ZHANG Chao-yun;HUANG Xian-zhang(Nanyang Institute of Technology,Zhang Zhongjing College of Chinese Medicine,Henan Nanyang 473000,China;Nanyang Institute of Technology,Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Henan Nanyang 473000,China)

机构地区：[1]南阳理工学院张仲景国医国药学院,河南南阳473000 [2]南阳理工学院河南省张仲景方药与免疫调节重点实验室,河南南阳473000

出　　处：《中国医院药学杂志》2020年第5期515-521,共7页Chinese Journal of Hospital Pharmacy

基　　金：河南省张仲景基金会资助项目。

摘　　要：目的:本研究采用网络药理学的方法,探讨大黄附子汤治疗慢性肾衰竭的药效物质基础、具体作用靶点及相关通路,构建"成分-靶点-通路"网络阐述大黄附子汤治疗慢性肾衰竭的作用机制。方法:通过文献和数据库查找大黄附子汤化学成分,采用类药性、药物动力学特征及适当的补偿机制对成分进行评估筛选;再依据反向药效团匹配预测大黄附子汤活性成分靶点,将筛选得到的活性成分和潜在靶点进行反向分子对接;通过DAVID数据库对靶点基因及相关通路注释分析,使用Cytoscape软件构建大黄附子汤抗CRF作用的"成分-靶点-通路"网络;最后通过ELISA的方法初步验证本研究结果的科学性和可靠性。结果:从大黄附子汤中共筛选出45个潜在活性化合物,预测存在17个潜在作用靶点。通过一系列的评估分析,最终筛选得到大黄附子汤治疗慢性肾衰竭的16个有效成分,6个作用靶点以及最具研究价值的5个通路;验证结果表明,所筛选成分中大黄素-8-葡萄糖苷、大黄酚-8-O-葡萄糖苷可与EGFR结合,初步证明本研究的意义。结论:大黄附子汤复方的配伍科学严谨,本研究为其治疗慢性肾衰竭提供现代研究支持,为其后续的开发提供科研基础,为中药复方的网络药理学的研究提供新参考。OBJECTIVE To explore the pharmacodynamic substance basis, specific targets and related pathways of Rhizome Aconiti Decoction(RAD)in treating chronic renal failure(CRF) by using the method of network pharmacology, and to construct a "component-target-pathway" network to elaborate the mechanism of RAD in treating CRF.METHODS The chemical constituents of RAD were searched through literature and database. The components were evaluated and screened by drug-likeness, ADMET and appropriate compensation mechanism. Then the target of RAD active ingredients was predicted based on reverse pharmacophore matching. and the selected active ingredients and potential targets were subjected to reverse molecular docking;the target genes and related pathways were annotated and analyzed by DAVID database, and the "component-target-pathway" network of Dahuang Fuzi Decoction against CRF was constructed using Cytoscape software;finally, the scientificity and reliability of the results of this study were preliminarily verified by ELISA.RESULTS A total of 45 potential active compounds and 17 potential targets were predicted from RAD. Through a series of evaluation and analysis, 16 active ingredients in RAD, 6 targets of RAD for CRF and 5 pathways with significant research value were finally screened. The verification test results showed that Emodin-8-Glucoside and Pulmatin could bind to EGFR, which preliminarily proved the significance of this study.CONCLUSION The compatibility of RAD compound is scientific and rigorous. This study provides modern research support for its treatment of CRF, lays a scientific research foundation for its follow-up development, and provides new reference for the research of network pharmacology of traditional Chinese medicine compound.

关 键 词：大黄附子汤 网络药理学 慢性肾衰竭 药效物质基础 作用机制 

分 类 号：R285[医药卫生—中药学]