鹿茸提取物抑制心肌肥厚的作用机制研究

摘要/Abstract

摘要： 目的：鉴于心肌肥厚作为心衰的重要风险因素，而中药领域对于心肌肥厚的研究尚显不足，本研究对鹿茸提取物在抑制心肌肥厚方面的潜在功效及其作用机制，特别是其可能的靶点进行探索。方法：本研究利用GEO数据库挖掘假手术与心肌肥厚小鼠心脏RNA测序基因集，通过Herb网站获取鹿茸靶基因，并运用DAVID平台进行差异基因通路富集分析。同时，采用Metascape对差异基因进行功能富集分析。为验证鹿茸提取物作用，构建Ang Ⅱ诱导的心肌细胞肥大模型，利用免疫荧光评估心肌细胞面积，并通过qRT-PCR检测心肌肥厚标志物BNP、β-MHC及鹿茸靶基因与心肌肥厚差异基因的共有基因表达。结果：从GEO数据库中成功挖掘到基因集GSE2459，该基因集与鹿茸靶基因存在4个共有基因。其中，3个基因在心肌肥厚模型中呈现上调表达，1个基因则表达下调。实验结果显示，鹿茸提取物能有效抑制Ang Ⅱ诱导的心肌细胞面积增大，同时降低心肌细胞中BNP和β-MHC的mRNA表达水平。此外，鹿茸提取物还能下调ATP13A3、NPY5R和HSD17B7的mRNA表达，并上调CRISP3的mRNA表达。结论：鹿茸提取物可以抑制Ang Ⅱ诱导的心肌肥厚，其潜在机制可能与调控共有靶基因ATP13A3、NPY5R、HSD17B7和CRISP3的表达有关。这可为鹿茸在心肌肥厚治疗中的应用提供依据，以期为中药防治心肌肥厚的研究提供思路。

关键词: font-size:medium, ">心肌肥厚；鹿茸；RNA测序；差异基因；共有基因

Abstract: Objective： Given that cardiac hypertrophy is an important risk factor for heart failure and research in the field of traditional Chinese medicine on cardiac hypertrophy remains insufficient， this study is dedicated to exploring the potential efficacy and mechanism of action of deer antler extract in inhibiting cardiac hypertrophy， especially its possible targets. Methods： In this study， the RNA sequencing gene sets of hearts from sham-operated and cardiac hypertrophy mice were mined using the GEO database. The target genes of deer antler were obtained through the Herb website， and differential gene pathway enrichment analysis was performed using the DAVID platform. Meanwhile， functional enrichment analysis of differential genes was carried out using Metascape. To verify the effect of deer antler extract， an Ang Ⅱ-induced cardiomyocyte hypertrophy model was constructed. The area of cardiomyocytes was evaluated by immunofluorescence， and the expression of common genes among the myocardial hypertrophy markers BNP， β-MHC， the target genes of deer antler， and the differential genes of myocardial hypertrophy was detected by qRT-PCR. Results： The gene set GSE2459 was successfully mined from the GEO database， and there were four common genes between this gene set and the target genes of deer antler. Among them， 3 genes showed up-regulated expression in the myocardial hypertrophy model， while 1 gene was down-regulated. The experimental results indicated that deer antler extract could effectively inhibit the increase in the area of cardiomyocytes induced by Ang Ⅱ and simultaneously reduce the mRNA expression levels of BNP and β-MHC in cardiomyocytes. In addition， deer antler extract could also down-regulate the mRNA expression of ATP13A3， NPY5R and HSD17B7， and up-regulate the mRNA expression of CRISP3. Conclusion： Deer antler extract can inhibit Ang Ⅱ-induced myocardial hypertrophy， and its potential mechanism may be related to the regulation of the expression of common target genes ATP13A3， NPY5R， HSD17B7 and CRISP3. This can provide a basis for the application of deer antler in the treatment of myocardial hypertrophy， hoping to open up a new direction for the research on the prevention and treatment of myocardial hypertrophy by traditional Chinese medicine.

Key words: font-size:medium, ">Cardiac hypertrophy； Deer antler； RNA sequencing； Differentially expressed genes； Shared genes

中图分类号:

李海艳1, 刘芮1, 崔悦1, 任婧1, 鄂明尧1, 赵磊2. 鹿茸提取物抑制心肌肥厚的作用机制研究[J]. 中国药物评价, 2025, 42(1): 28-34.

LI Haiyan1, LIU Rui1, CUI Yue1, REN Jing1, E Mingyao1, ZHAO Lei2. The Effect of Deer Antler Extract on Inhibiting Cardiac Hypertrophy[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2025, 42(1): 28-34.

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