中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (12): 3044-3057.doi: 10.12307/2026.665

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

韭菜子有效成分多靶点干预少弱精子症模型大鼠的作用机制

姜欢欢1，2，穆  胜1，2，马文欣3，刘  畅3，刘自钰3，蒲  静3，朱向东1，2，惠  宏1，2，马会明3   

  1. 宁夏医科大学，1中医学院，2宁夏少数民族现代化教育部重点实验室，3生育力保持教育部重点实验室，宁夏回族自治区银川市  750004

  • 收稿日期:2025-06-30 接受日期:2025-07-31 出版日期:2026-04-28 发布日期:2025-09-29
  • 通讯作者: 马会明，教授，硕士生导师，宁夏医科大学生育力保持教育部重点实验室，宁夏回族自治区银川市 750004 共同通讯作者：惠宏，硕士，教授，硕士生导师，宁夏医科大学中医学院，宁夏少数民族现代化教育部重点实验室，宁夏回族自治区银川市 750004
  • 作者简介:姜欢欢，女，1993年生，宁夏回族自治区石嘴山市人，汉族，宁夏医科大学在读硕士，主要从事生殖与内分泌研究。
  • 基金资助:
    国家自然科学基金面上资助项目(82274624)，项目负责人：马会明

Mechanism of multi-target intervention of the active ingredient of Allii Tuberosi Semen in rats with oligoasthenozoospermia

Jiang Huanhuan1, 2, Mu Sheng1, 2, Ma Wenxin3, Liu Chang3, Liu Ziyu3, Pu Jing3, Zhu Xiangdong1, 2, Hui Hong1, 2, Ma Huiming3   

  1. 1College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 2Key Laboratory of Modernization of Traditional Medicine for Ethic Minorities in Ningxia, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3Key Laboratory of Fertility Maintenance, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2025-06-30 Accepted:2025-07-31 Online:2026-04-28 Published:2025-09-29
  • Contact: Ma Huiming, Professor, Master’s supervisor, Key Laboratory of Fertility Maintenance, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China Co-corresponding author: Hui Hong, MS, Professor, Master’s supervisor, College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Modernization of Traditional Medicine for Ethic Minorities in Ningxia, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Jiang Huanhuan, MS candidate, College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Modernization of Traditional Medicine for Ethic Minorities in Ningxia, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China (General Program), No. 82274624 (to MHM)

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摘要：


文题释义：
网络药理学：该方法整合药物结构特征与疾病相关基因信息，构建“药物-成分-靶点-疾病”多维互作网络，旨在系统解析活性成分、识别潜在作用靶点、筛选关键调控通路，以优化治疗效能并减轻不良反应。
分子对接：分子对接技术的理论渊源可追溯至1894年Fisher提出的“锁钥模型”(Lock-and-key model)，其核心机制在于阐释生物大分子与小分子配体通过三维空间互补性及分子间作用力实现特异性结合。

背景：目前针对少弱精子症的治疗措施仍然有限，大多数植物中草药不良反应小且来源丰富，为治疗少弱精子症提供了新的思路和方法。
目的：采用网络药理学方法探讨韭菜子改善雷公藤多苷片诱导少弱精子症模型大鼠精子生成及质量的作用机制，并进行动物实验验证。
方法：整合网络药理学与生物信息学方法，系统解析韭菜子治疗雷公藤多苷片诱导少弱精子症模型大鼠的分子机制：基于TCMSP、Genecards等数据库交叉筛选获得韭菜子活性成分靶点与少弱精子症疾病靶点，取韦恩交集得到核心作用靶点；通过Cytoscape构建药物-成分-靶点-疾病网络，结合STRING数据库构建蛋白质互作网络，基于拓扑参数筛选出前10位核心靶点；采用DAVID进行基因本体(GO)功能、京都基因与基因组百科全书通路(KEGG)富集分析，揭示韭菜子通过调控磷脂酰肌醇3激酶/蛋白激酶B信号通路发挥治疗作用，利用CB-Dock2在线网站进行分子对接计算动力结合能。采用动物实验进一步验证韭菜子改善雷公藤多苷片诱导少弱精子症模型大鼠精子生成及质量的作用机制。
结果与结论：①网络药理学提示，韭菜子筛选出16个有效成分，疾病靶点为1 095个；②蛋白质互作网络筛出10个核心靶点；③基因本体、京都基因与基因组百科全书通路富集分析结果显示，主要集中磷脂酰肌醇3激酶/蛋白激酶B信号通路；④磷脂酰肌醇3激酶/蛋白激酶B信号通路关键蛋白丝氨酸激酶1、B细胞淋巴瘤2、白细胞介素6、表皮生长因子受体、糖原合酶激酶3β与槲皮素、山奈酚及亚油酸进行分子对接；⑤动物实验结果表明，经过韭菜子治疗后少弱精子症模型组大鼠的睾丸质量、精子计数及前向运动精子比例均显著增加，能有效改善少弱精子症模型大鼠的组织病理学表现，磷酸化磷脂酰肌醇3激酶、磷酸化蛋白激酶B、B细胞淋巴瘤2蛋白表达显著上调，睾丸组织细胞凋亡率明显降低。结果表明：韭菜子可能通过调控磷脂酰肌醇3激酶/蛋白激酶B通路改善雷公藤多苷片诱导的少弱精子症大鼠精子生成及质量。
https://orcid.org/0009-0004-5103-1947(姜欢欢)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 韭菜子, 少弱精子症, 网络药理学, 动物实验, 磷脂酰肌醇3激酶(PI3K), 蛋白激酶B(AKT), 凋亡, 分子对接, 药食同源

Abstract: BACKGROUND: Current therapeutic measures for oligoasthenozoospermia remain limited, while botanical herbal medicines with minimal adverse reactions and abundant sources provide novel insights and approaches for the treatment of oligoasthenozoospermia.
OBJECTIVE: To investigate the mechanism of Allii Tuberosi Semen in improving spermatogenesis and quality in a rat model of oligoasthenozoospermia induced by tripterygium glycoside tablets using network pharmacology, and to conduct experimental verification.
METHODS: This study integrated network pharmacology and bioinformatics approaches to systematically investigate the molecular mechanisms underlying the therapeutic effects of Allii Tuberosi Semen intervention in the rat model of oligoasthenozoospermia induced by tripterygium glycoside. Specifically, active ingredient targets of Allii Tuberosi Semen and oligoasthenozoospermia-associated disease targets were identified through cross-database screening (TCMSP, Genecards, etc.), followed by Venn intersection analysis to pinpoint core therapeutic targets. The drug-component-target-disease network was constructed by Cytoscape, the protein-protein interaction network was constructed in combination with the STRING database, and the top 10 core targets were screened based on topological parameters. DAVID was used to analyze the enrichment of gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway, revealing that Allii Tuberosi Semen played a therapeutic role by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) signaling pathway, and CB-Dock2 was used to calculate the kinetic binding energy by molecular docking. Animal experiments were conducted to further verify the mechanism by which Allii Tuberosi Semen improves spermatogenesis and sperm quality in the rat model of oligoasthenozoospermia induced by tripterygium glycoside.
RESULTS AND CONCLUSION: (1) Network pharmacology analysis revealed that Allii Tuberosi Semen contain 16 bioactive compounds, with 1 095 disease-associated targets identified through systematic screening. (2) The protein-protein interaction network screened out 10 core targets. (3) Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated significant enrichment in the PI3K/AKT signaling pathway. (4) Molecular docking analysis was performed between key targets of the PI3K/AKT signaling pathway (serine kinase 1, B lymphoblastoma 2 protein, interleukin 6, epidermal growth factor receptor, and glycogen synthase kinase 3β) and the bioactive compounds quercetin, kaempferol, and linoleic acid. (5) Animal experiments demonstrated that treatment with Allii Tuberosi Semen significantly improved testicular weight, sperm count, and the proportion of sperm with progressive motility in the rat model of oligoasthenospermia. It effectively ameliorated histopathological manifestations in the testes and modulated the expression of phosphorylated PI3K, phosphorylated AKT, and B lymphoblastoma 2 protein, resulting in a significant reduction in the testicular tissue apoptosis rate. These findings suggest that Allii Tuberosi Semen may improve spermatogenesis and sperm quality in the tripterygium glycoside-induced oligoasthenospermia rat model by regulating the PI3K/AKT pathway.

Key words: Allii Tuberosi Semen, oligoasthenozoospermia, network pharmacology, animal experiment, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), apoptosis, molecular docking, homology of medicine and food

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