龙胆泻肝汤改善多囊卵巢综合征作用机制的网络药理学分析及实验验证*

作者：唐 雨1，张家乐2，吴星霏2，谢秉恒2，吴刘俊2，申艳朵2，张明昊3，马丽亚4

单位：1.河南中医药大学第二临床医学院，河南 郑州 450046； 2.河南中医药大学第五临床医学院，河南 郑州 450046； 3.河南中医药大学医学院，河南 郑州 450046； 4.河南中医药大学教务部，河南 郑州 450046

引用：引用：唐雨，张家乐，吴星霏，谢秉恒，吴刘俊，申艳朵，张明昊，马丽亚.龙胆泻肝汤改善多囊卵巢综合征作用机制的网络药理学分析及实验验证[J].中医药导报,2025,31(8):5-11.

DOI：10.13862/j.cn43-1446/r.2025.08.002

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摘要：

目的：探讨龙胆泻肝汤改善多囊卵巢综合征（PCOS）的分子机制。方法：（1）网络药理学。通过数据库得到龙胆泻肝汤组方中药作用靶点和PCOS疾病靶点，取交集。运用Cytoscape 3.6.1构建互作网络。通过David数据库富集分析，并进行分子对接验证。（2）实验验证。建立来曲唑诱导的PCOS大鼠模型，将造模成功大鼠随机分组，采用酶联免疫吸附试验（ELISA）检测血清性激素水平，计算卵巢系数。采用苏木素-伊红HE染色观察卵巢形态学改变，运用免疫组织化学（IHC）染色法检测关键蛋白表达。结果：（1）网络药理学分析共得到龙胆泻肝汤活性成分123个，筛选出龙胆泻肝汤改善PCOS的潜在作用靶点192个，4个关键活性成分（山柰酚、汉黄芩素、槲皮素、木犀草素），3个核心靶点（TP53、TNF-α、IL-6），分子对接显示关键活性成分与核心靶点之间具有较强的结合力；GO功能富集分析得到774个功能条目，KEGG通路富集分析得到158个通路。（2）实验结果显示，与空白组（KB组）比较，模型组（MX组）大鼠血清E2、FSH水平降低（P＜0.05），T、GnRH、LH蛋白表达升高（P＜0.05），卵巢系数升高（P＜0.05），卵巢组织中囊性卵泡增多，卵泡颗粒细胞层数减少，TP53蛋白表达降低（P＜0.05），TNF-α、IL-6蛋白表达升高（P＜0.05）；与MX组比较，各给药干预组大鼠血清E2、FSH蛋白表达升高（P＜0.05），T、GnRH、LH蛋白表达降低（P＜0.05），卵巢系数降低（P＜0.05），卵巢组织囊性病变明显减轻，卵巢中TP53蛋白表达升高（P＜0.05），TNF-α、IL-6蛋白表达降低（P＜0.05）。结论：龙胆泻肝汤可有效改善PCOS大鼠内分泌紊乱及卵巢组织病理状态，其作用可能是通过上调TP53蛋白表达、下调TNF-α、IL-6蛋白表达实现的。

关键词：多囊卵巢综合征；龙胆泻肝汤；网络药理学；实验验证；大鼠

Abstract：

Objective: To explore the molecular mechanism underlying the improvement of polycystic ovary syndrome (PCOS) by Longdan Xiegan decoction. Methods: (1) Network Pharmacology. The target points of the traditional Chinese medicine ingredients in Longdan Xiegan decoction and those of PCOS were obtained from databases, and their intersection was determined. The interaction network was constructed using Cytoscape 3.6.1. Enrichment analysis was conducted via the David database and verified through molecular docking. (2) Experimental Verification. A PCOS animal model induced by letrozole was established. The successfully modeled rats were randomly grouped. The serum sex hormone levels were detected by enzyme-linked immunosorbent assay (ELISA), and the ovarian coefficient was calculated. Hematoxylin-eosin staining (HE) was employed to observe the morphological changes of the ovaries, and the expression of key proteins was detected by immunohistochemistry (IHC) staining. Results: (1) Through network pharmacology analysis, 123 active components of Longdan Xiegan decoction were identified, and 192 potential target points for improving PCOS were screened out. There were 4 key active components, including kaempferol, wogonin, quercetin, and luteolin. There were 3 core target points, including TP53, TNFα, and IL6. Molecular docking indicated a strong binding force between them. Gene ontology (GO) functional analysis yielded 774 functional items and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis yielded 158 pathways. (2) The experimental results revealed that compared with the normal group (KB group), the serum E2 and FSH levels in the model group (MX group) decreased (P<0.05), while the T, GnRH, and LH levels increased (P<0.05), and that the ovarian coefficient increased (P<0.05). There was an increase in cystic follicles in the ovarian tissue, a reduction in the number of granulosa cell layers, a decrease in the TP53 level (P<0.05), and an increase in the TNF-α and IL-6 levels in MX group (P<0.05). Compared with the MX group, the serum E2 and FSH levels of the rats increased in each drug intervention group (P<0.05), while the T, GnRH, and LH levels decreased (P<0.05). The ovarian coefficient decreased (P<0.05), and the cystic lesions in the ovarian tissue were significantly alleviated in each drug intervention group. The TP53 level in the ovary increased (P<0.05), while the TNF-α and IL-6 levels decreased in each drug intervention group (P<0.05). Conclusion: Longdan Xiegan decoction can effectively improve the endocrine disorder and pathological state of the ovarian tissue in PCOS rats, and its effect may be achieved by up-regulating the TP53 level and down-regulating the TNF-α and IL-6 levels.

Key words：polycystic ovary; Longdan Xiegan decoction; network pharmacology; experimental verification; rat

发布时间：2026-01-06

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