| 张杨,姚美玉,谷玥儒,等.大黄素抗多囊卵巢综合征:凋亡通路和激素调节[J].安徽医药,2026,30(1):54-59. |
| 大黄素抗多囊卵巢综合征:凋亡通路和激素调节 |
| Exploring the anti-PCOS effects of emodin: insights into apoptosis pathway and hormone regulation |
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| DOI：10.3969/j.issn.1009-6469.2026.01.012 |
| 中文关键词: 大黄素 多囊卵巢综合征 雌激素受体 2 雌激素 网络药理学 小鼠，近交 C57BL |
| 英文关键词: Emodin Polycystic ovary syndrome Estrogen receptor 2 Estrogen Network pharmacology Mice, inbred C57BL |
| 基金项目:国家自然科学基金资助项目( 81804138；82174195)；自然基金课题中国博士后科学基金项目( 2019M661320)； |
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| 中文摘要: |
| 目的探讨大黄素对多囊卵巢综合征( PCOS)小鼠模型性激素水平及雌激素受体 2(ESR2)表达的影响，揭示其潜在的治疗机制。方法将 30只 4周龄雌性 C57BL/6J小鼠以随机数字表法进行分组，分为正常组、模型组( PCOS)以及治疗组［大黄素， 25 mg·kg.1·d.1］，各 10只(研究时间为 2022年 5月 30日至 2023年 6月 30日)。除正常组外，其余各组采用去氢表雄酮( dehy-droepiandrosterone，DHEA，6 mg·kg.1·d.1)诱导的 PCOS小鼠模型；造模成功后，连续给予治疗组 14 d大黄素 8.75 mg·kg.1·d.1后，称得体质量后麻醉处死小鼠取血，分离卵巢组织，观察小鼠体质量、卵巢质量、计算卵巢质量指数；以酶联免疫吸附分析( ELI-SA)检测小鼠血清中血清黄体生成素( LH)、卵泡刺激素( FSH)和雄激素的表达水平；以苏木精 -伊红染色以及免疫组织化学法检测卵巢组织形态以及 ESR2的表达。应用网络药理学的方法分析大黄素以及 PCOS作用靶点。同时，借助 STRING数据库构建蛋白相互作用网络以及通过 Cytoscape软件获得 "药物 -疾病 -核心靶基因”网络。基因本体和京都基因与基因组百科全书富集分析预测大黄素抗 PCOS的下游通路。分子对接分析大黄素与 ESR2蛋白的潜在结合能力。结果大黄素能够逆转由 PCOS导致的小鼠体质量、卵巢质量和卵巢质量指数升高；同时，使血清中 LH及雄激素水平显著降低， FSH水平显著升高； ESR2蛋白表达水平增加。网络药理学结果表明，大黄素与 PCOS有 36个共同靶点，其中雌激素受体 1、糖原合成酶激酶 3β、表皮生长因子受体、雌激素受体 2、热休克蛋白 90α、芳香化酶、细胞周期蛋白依赖激酶表达最为丰富。 KEGG通路富集筛选出雌激素信号通路、胰岛素抵抗信号通路以及神经营养因子信号通路等是大黄素抗 PCOS潜在的作用通路。分子对接显示 ESR2与大黄素有较好的结合性( .31.80 kJ/mol)。且免疫组织化学法进一步表明模型组中 ESR2表达明显降低，而大黄素能够使 ESR2表达上调。结论大黄素能够通过调控 ESR2表达来逆转由 DHEA导致 PCOS小鼠体内性激素水平异常，以及卵巢功能损伤。 |
| 英文摘要: |
| Objective To explore the effects of emodin on the sex hormone levels and the expression of estrogen receptor 2 (ESR2) ina mouse model of polycystic ovary syndrome (PCOS), and to reveal its potential therapeutic mechanism.Methods From May 30, 2022 to June 30, 2023, Thirty 4-week-old female C57BL/6J mice were randomly (random number method) allocated into three groups byweight: control group, PCOS group, and Emodin group (8.75 mg·kg.1 ·d.1), with each group comprising 10 mice. PCOS was induced inthe groups, except for the control group, through dehydroepiandrosterone (DHEA, 6 mg·kg.1·d.1) administration. Following successfulmodeling Emodin was administered for a duration of 14 days. Subsequently, the mice were euthanized, blood samples were collected,and ovarian tissues were isolated to assess body weight, ovarian weight, and calculate the ovarian weight index. Enzyme-linked immuno-sorbent assay (ELISA) was employed to determine the expression levels of luteinizing hormone (LH), follicle-stimulating hormone(FSH), and testosterone (T) in mouse serum. Morphology of ovarian tissue and the expression of ESR2 were evaluated using hematoxylinand eosin (H&E) staining and immunohistochemistry, respectively. Network pharmacology analysis was conducted to identify Emodin's targets and its role in PCOS. Additionally, a protein-protein interaction network and a "drug-disease-core target gene" network wereconstructed using the STRING database and Cytoscape software, respectively. GO and KEGG enrichment analyses were performed topredict downstream pathways implicated in Emodin 's anti-PCOS effects. Molecular docking analysis was executed to explore the poten-tial binding affinity between Emodin and ESR2 protein.Results Emodin reversed the elevated body weight, ovarian weight, and ovari-an weight index induced by PCOS in mice. Furthermore, it notably reduced LH and T levels in serum while significantly increasingFSH levels. ESR2 protein expressions were upregulated. Network pharmacology analysis indicated that Emodin shared 36 common tar-gets with PCOS, including highly expressed targets like ESR1, GSK3B, EGFR, ESR2, HSP90AA1, CYP19A1, and CDK5. KEGG path-way enrichment analysis identified potential pathways involved in Emodin's anti-PCOS effects, such as the estrogen signaling pathway,insulin resistance signaling pathway, and neurotrophic factor signaling pathway. Molecular docking analysis revealed a favorable bind-ing affinity (-31.80 kJ/mol) between ESR2 and Emodin. Immunohistochemistry further validated a significant decrease in ESR2 expres-sion in the PCOS group, which was upregulated by Emodin.Conclusion Emodin can ameliorate abnormal hormone levels and ovarian dysfunction induced by DHEA in PCOS mice by modulating ESR2 expression. |
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