[1]范巧明,罗冬强,蔡惠连,等.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[J].国际内分泌代谢杂志,2024,44(03):155-160.[doi:10.3760/cma.j.cn121383-20231022-10037]
 Fan Qiaoming,Luo Dongqiang,Cai Huilian,et al.Based on bioinformatics analysis and experimental verification, the composition and mechanism of TCM anti-diabetic nephropathy were discussed[J].International Journal of Endocrinology and Metabolism,2024,44(03):155-160.[doi:10.3760/cma.j.cn121383-20231022-10037]
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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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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
44
期数:
2024年03期
页码:
155-160
栏目:
论著
出版日期:
2024-05-20

文章信息/Info

Title:
Based on bioinformatics analysis and experimental verification, the composition and mechanism of TCM anti-diabetic nephropathy were discussed
作者:
范巧明1罗冬强1蔡惠连1刘曼婷1刘峰2
1广州中医药大学,广州 511000; 2广州中医药大学第三附属医院,广州 511000
Author(s):
Fan Qiaoming1 Luo Dongqiang1 Cai Huilian1 Liu Manting1 Liu Feng2.
1Guangzhou University of Chinese Medicine, Guangzhou 511000, China; 2The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 511000, China
关键词:
糖尿病肾脏病 数据挖掘 生物信息学 动物实验
Keywords:
Diabetic nephropathy Data mining Bioinformatics Animal experiments
DOI:
10.3760/cma.j.cn121383-20231022-10037
摘要:
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。
Abstract:
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-confidence 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 Network(WGCNA)and machine learning. genes and validate the expression differences of hub genes.Results The combination of “Astragalus-Salvia-Cornus 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 tissue was improved compared with the model group.Conclusion As a new formula, “Astragalus-Salvia-Cornus 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 basis for the subsequent drug development and clinical application of DKD.

参考文献/References:

[1] Zhang L,Long J,Jiang W,et al.Trends in chronic kidney disease in China[J].N Engl J Med, 2016,375(9):905-906.DOI:10.1056/NEJMc1602469.
[2] Gheith O,Farouk N,Nampoory N,et al.Diabetic kidney disease: world wide difference of prevalence and risk factors[J].J Nephropharmacol,2015,5(1):49-56.
[3] Stenvinkel P.Chronic kidney disease:a public health priority and harbinger of premature cardiovascular disease[J].J Intern Med,2010,268(5):456-467.DOI:10.1111/j.1365-2796.2010.02269.x.
[4] 庞天霄,吴希泽,孙晓芳,等.糖肾平膏治疗糖尿病肾病的临床疗效观察[J].中华中医药学刊,2022,40(4):85-88.DOI:10.13193/j.issn.1673-7717.2022.04.017.
[5] 张圣英,尹长江,刘喜纲,等.中医药治疗糖尿病肾脏纤维化研究进展[J].中国实验方剂学杂志,2022,28(11):275-282.DOI:10.13422/j.cnki.syfjx.20220505.
[6] 董俊平,霍曼.丹芪益肾方治疗气阴两虚夹瘀型糖尿病肾病[J].中医学报,2019,34(6):1304-1308.DOI:10.16368/j.issn.1674-8999.2019.06.310.
[7] 王文儒,丁晓庆,杨秀鹏,等.补肾健脾方对再生障碍性贫血患者细胞自噬的影响[J].中国实验方剂学杂志,2023,29(14):80-87.DOI:10.13422/j.cnki.syfjx.20231190.
[8] 曹放,何兴伟,郭翠,等.基于数据挖掘及网络药理学方法探讨血管性痴呆用药规律及机制研究[J].中医临床研究,2022,14(28):18-24.DOI:10.3969/j.issn.1674-7860.2022.28.004.
[9] 李荣萍.糖尿病肾病患者的中医治疗方法及效果研究[J].中医临床研究,2018,10(1):60-61.
[10] Xu Z,Xiang X,Su S,et al.Multi-omics analysis reveals the pathogenesis of db/db mice diabetic kidney disease and the treatment mechanisms of multi-bioactive compounds combination from Salvia miltiorrhiza[J].Front Pharmacol,2022,13:987668.DOI:10.3389/fphar.2022.987668.
[11] Qian X,He L,Hao M,et al.YAP mediates the interaction between the Hippo and PI3K/Akt pathways in mesangial cell proliferation in diabetic nephropathy[J].Acta diabetologica,2021,58(1):47-62.DOI:10.1007/s00592-020-01582-w.
[12] 孙凤起,武韧,常贵全,等.肾小球系膜细胞增殖在糖尿病肾病肾小球硬化中作用的研究进展[J].基础医学与临床,2021,41(10):1510-1513.DOI:10.16352/j.issn.1001-6325.2021.10.031.
[13] Yang T,Heng C,Zhou Y,et al.Targeting mammalian serine/threonine-protein kinase 4 through Yes-associated protein/TEA domain transcription factor-mediated epithelial-mesenchymal transition ameliorates diabetic nephropathy orchestrated renal fibrosis[J].Metabolism:clinical and experimental,2020,108:154258.DOI:10.1016/j.metabol.2020.154258.
[14] Szeto SG,Narimatsu M,Lu M,et al.YAP/TAZ are mechanoregulators of TGF-β-Smad signaling and renal fibrogenesis[J].J Am Soc Nephrol,2016,27(10):3117-3128.DOI:10.1681/ASN.2015050499.
[15] Wang S,Wu X,Lincoln TM,et al.Expression of constitutively active cGMP-dependent protein kinase prevents glucose stimulation of thrombospondin 1 expression and TGF-beta activity[J].Diabetes,2003,52(8):2144-2150.DOI:10.2337/diabetes.52.8.2144.
[16] Maimaitiyiming H,Li Y,Cui W,et al.Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function[J].Am J Physiol Renal Physiol,2013,305(6):F881-F890.DOI:10.1152/ajprenal.00192.2013.
[17] Qi H,Casalena G,Shi S,et al.Glomerular endothelial mitochondrial dysfunction is essential and characteristic of diabetic kidney disease susceptibility[J].Diabetes,2017,66(3):763-778.DOI:10.2337/db16-0695.

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备注/Memo

备注/Memo:
通信作者:刘峰,Email:lftcm@163.com
更新日期/Last Update: 2024-05-30