糖尿病心肌病潜在治疗药物的鉴定

IF 2.9 4区 医学 Q1 Medicine
Z. You, Yunhong Wang, Lin Huang
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引用次数: 0

摘要

本研究的重点是确定糖尿病心肌病(DCM)的潜在治疗药物和作用机制。利用 GSE197850 数据集中的基因表达谱,我们应用加权相关网络分析、Limma 和基因组变异分析 (GSVA) 发现了与 DCM 相关的基因组和通路。随后,我们利用 String 进行了蛋白质相互作用网络分析,并通过 Cytoscape 发现了 10 个枢纽基因:ACTN2、ITGA1、CASP3、PXN、PCNA、CAV1、GAPDH、FEN1、PTPN11 和 ESR1。使用大鼠 H9C2 心肌细胞进行的体外验证显示,在高葡萄糖条件下,FEN1、PCNA、PTPN11、CAV1、GAPDH、CASP3、PXN 和 ACTN2 上调,ESR1 和 ITGA11 下调。我们还利用 CIBERSORT 进行了免疫浸润分析,并利用 Autodock Vina 进行了分子对接,以探索潜在的治疗药物。我们的研究结果发现,雌二醇、丙戊酸、对乙酰氨基酚和白藜芦醇是治疗 DCM 的潜在药物。其中,白藜芦醇具有促进自噬的作用。本研究利用全面的生物信息学和实验方法精确定位了 DCM 相关基因,阐明了关键枢纽基因,并提出白藜芦醇是治疗 DCM 的潜在药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Potential Therapeutic Drugs for Diabetic Cardiomyopathy
This study focused on identifying potential therapeutic drugs and mechanisms of action for diabetic cardiomyopathy (DCM). Using gene expression profiles from the GSE197850 dataset, we applied Weighted Correlation Network Analysis, Limma, and Gene Set Variation Analysis (GSVA) to uncover DCM-related gene sets and pathways. Subsequently, we conducted protein interaction network analysis with String and identified 10 hub genes through Cytoscape: ACTN2, ITGA1, CASP3, PXN, PCNA, CAV1, GAPDH, FEN1, PTPN11, and ESR1. In vitro validation using Rat H9C2 cardiomyocytes showed upregulation of FEN1, PCNA, PTPN11, CAV1, GAPDH, CASP3, PXN, and ACTN2, and downregulation of ESR1 and ITGA11 in high-glucose conditions. We further performed immune infiltration analysis with CIBERSORT and explored potential therapeutic agents through molecular docking with Autodock Vina. Our findings identified estradiol, valproic acid, acetaminophen, and resveratrol as potential drugs for DCM. Among these, resveratrol showed promise by promoting autophagy. This study leveraged comprehensive bioinformatic and experimental methods to pinpoint DCM-related genes, elucidate key hub genes, and propose resveratrol as a latent drug for DCM.
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来源期刊
CiteScore
4.30
自引率
17.20%
发文量
145
审稿时长
2.3 months
期刊介绍: Information not localized
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