首页|基于生信分析及实验验证探讨中医药抗糖尿病肾脏病的组方规律及作用机制

基于生信分析及实验验证探讨中医药抗糖尿病肾脏病的组方规律及作用机制

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目的 探索中医药抗糖尿病肾脏病(DKD)的用药规律和作用机制,并通过动物实验验证.方法 收集中医药抗DKD的文献报道,提取方药信息,筛选高置信度和支持度药物组合作为新方,并获取新方的活性成分及作用靶点;从GEO数据库获取DKD相关的数据集GSE30122和GSE30529,联合加权基因共表达网络(WGCNA)和机器学习鉴定新方抗DKD的关键基因(hub genes),并验证hub genes的表达差异.结果 药物组合"黄芪-丹参-山茱萸"作为新方,涉及靶点1 378个,基于GSE30122和GSE529,进一步获得新方与疾病共同作用靶点19个,作用靶点主要富集于Hippo信号通路、环磷酸鸟苷/蛋白激酶-G信号通路等;最终筛选出2个hub genes:EDNRA和HDAC9.与对照组相比,hub genes在模型组具有更高的表达,且肾组织损伤更甚;经新方干预,治疗组有效降低了 hub genes的表达量,且肾组织较模型组改善.结论 "黄芪-丹参-山茱萸"作为新方,可能通过EDNRA和HDAC9,调节Hippo、cGMP-PKG等信号通路抑制肾损伤,进而发挥DKD的治疗作用,为后续治疗DKD的药物开发和临床应用提供理论基础.
Based on bioinformatics analysis and experimental verification,the composition and mechanism of TCM anti-diabetic nephropathy were discussed
Objective To explore the medication rules and mechanism of anti-diabetic nephropathy(DKD)in traditional Chinese medicine,and verify it through animal experiments.Methods We collected the literature reports on anti-DKD in TCM,extracted the information of formulas,screened the high-confi-dence and supportive drug combinations as new formulas,and obtained the active ingredients and targets of the new formulas;we obtained the DKD-related datasets GSE30122 and GSE30529 from the GEO database,and identified the new formulas'anti-DKD hub genes by combining the Weighted Gene Co-Expression Net-work(WGCNA)and machine learning.genes and validate the expression differences of hub genes.Results The combination of"Astragalus-Salvia-Comus officinalis"as a new formula involves 1,378 targets.Based on GSE30122 and GSE529,19 targets were further obtained,and the targets were mainly enriched in the Hippo signaling pathway,cGMP-PKG signaling pathway,etc.and finally,we screened out two hub genes:EDNRA and HDAC9.EDNRA and HDAC9.Compared with the control group,the expression of Hub Genes was higher in the model group,and the renal tissue damage was more severe,and the expression of Hub Genes was effectively reduced in the treatment group after the intervention of Xinfang,and the renal tis-sue was improved compared with the model group.Conclusion As a new formula,"Astragalus-Salvia-Cor-nus officinalis"may inhibit kidney injury by regulating Hippo,cGMP-PKG,and other signaling pathways through EDNRA and HDAC9,thereby exerting the therapeutic effect of DKD and providing a theoretical ba-sis for the subsequent drug development and clinical application of DKD.

Diabetic nephropathyData miningBioinformaticsAnimal experiments

范巧明、罗冬强、蔡惠连、刘曼婷、刘峰

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广州中医药大学,广州 511000

广州中医药大学第三附属医院,广州 511000

糖尿病肾脏病 数据挖掘 生物信息学 动物实验

2024

国际内分泌代谢杂志
中华医学会,天津医科大学

国际内分泌代谢杂志

CSTPCD
影响因子:0.842
ISSN:1673-4157
年,卷(期):2024.44(3)
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