生物信息学分析筛选畸形精子症氧化应激关键基因及候选中药材预测

doi:10.12280/gjszjk.20250163

摘要/Abstract

摘要：

目的：利用生物信息学分析筛选畸形精子症与氧化应激相关的差异表达基因（differentially expressed genes related to oxidative stress，OS-DEG）并进行候选中药材预测。方法：从GEO（Gene Expression Omnibus）数据库查找GSE6969基因表达图谱，筛选差异表达基因后与GeneCards数据库中OS-DEG取交集，通过基因本体（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析以及蛋白质-蛋白质互作（protein-protein interaction，PPI）网络筛选关键通路和基因，在中医药百科全书数据库（The Encyclopedia of Traditional Chinese Medicine，ETCM）中查找关键基因的候选中药材药物。结果：通过差异分析共发现261个OS-DEG，利用Cytoscape筛选出PTEN、JUN、糖原合成酶激酶3β（glycogen synthase kinase 3β，GSK3β）、超氧化物歧化酶2（superoxide dismutase 2，SOD2）等关键基因。预测的候选靶向中药材包括马齿苋、北沙参、半夏、马鞭草、丹参和白附子等。结论：可利用生物信息学分析筛选畸形精子症氧化应激相关的基因，为探讨中医药治疗畸形精子症提供新的见解。

关键词: 畸形精子症, 氧化性应激, 基因, 中草药, 生物信息分析

Abstract:

Objective: To identify the oxidative stress-related key genes that differentially expressed (OS-DEG) in teratozoospermia through bioinformatics analysis, and to predict the candidate targeted Chinese herbal medicines. Methods: The GSE6969 gene expression profile from the GEO (Gene Expression Omnibus) database was retrieved, and the differentially expressed genes were screened. These genes were then intersected with the oxidative stress-related genes that retrieved from the GeneCards database. The key pathways and genes were identified through Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis. Finally, the potential candidate herbal medicines targeting those key genes were searched from the Encyclopedia of Traditional Chinese Medicine (ETCM) database. Results: A total of 261 OS-DEGs Key genes were identified by differential analysis, including PTEN, JUN, glycogen synthase kinase 3β (GSK3β), and superoxide dismutase 2 (SOD2) were screened using Cytoscape. The candidate Chinese herbal medicines were identified, such as Portulaca oleracea, Glehnia littoralis, Pinellia ternata, Verbena officinalis, Salvia miltiorrhiza, Typhonium giganteum. Conclusions: In this study, bioinformatics analysis was used to screen the genes related to oxidative stress in teratozoospermia, which provided a new insight into the treatment of teratozoospermia with traditional Chinese medicine.

Key words: Teratozoospermia, Oxidative stress, Genes, Drugs, Chinese herbal, Bioinformatics analysis

杜超, 侯开波, 关小川, 王博伦, 吴莹, 于月新. 生物信息学分析筛选畸形精子症氧化应激关键基因及候选中药材预测[J]. 国际生殖健康/计划生育杂志, 2025, 44(5): 361-365.

DU Chao, HOU Kai-bo, GUAN Xiao-chuan, WANG Bo-lun, WU Ying, YU Yue-xin. Bioinformatics Analysis to Identify Oxidative Stress-Related Key Genes in Teratozoospermia and Predict Candidate Traditional Chinese Herbal Medicines[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(5): 361-365.

图/表 4

参考文献 23

[1]	Eisenberg ML, Esteves SC, Lamb DJ, et al. Male infertility[J]. Nat Rev Dis Primers, 2023, 9(1):49. doi: 10.1038/s41572-023-00459-w. pmid: 37709866
[2]	Arora M, Mehta P, Sethi S, et al. Genetic etiological spectrum of sperm morphological abnormalities[J]. J Assist Reprod Genet, 2024, 41(11):2877-2929. doi: 10.1007/s10815-024-03274-8.
[3]	Agarwal A, Tvrda E, Sharma R. Relationship amongst teratozoospermia, seminal oxidative stress and male infertility[J]. Reprod Biol Endocrinol, 2014,12:45. doi: 10.1186/1477-7827-12-45.
[4]	Ammar O, Mehdi M, Muratori M. Teratozoospermia: Its association with sperm DNA defects, apoptotic alterations, and oxidative stress[J]. Andrology, 2020, 8(5):1095-1106. doi: 10.1111/andr.12778. pmid: 32096605
[5]	Kaltsas A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants[J]. Medicina(Kaunas), 2023, 59(10):1769. doi: 10.3390/medicina59101769.
[6]	Buhling K, Schumacher A, Eulenburg CZ, et al. Influence of oral vitamin and mineral supplementation on male infertility: a meta-analysis and systematic review[J]. Reprod Biomed Online, 2019, 39(2):269-279. doi: 10.1016/j.rbmo.2019.03.099. pmid: 31160241
[7]	Tang Z, Ding W, Wang L, et al. Protective effect of vitamin E on methyl methanesulfonate-induced teratozoospermia in adult Sprague-Dawley rats[J]. Mol Med Rep, 2015, 12(3):4422-4426. doi: 10.3892/mmr.2015.3916. pmid: 26062593
[8]	祝浩然, 陈知絮, 郝高利, 等. 基于文献数据挖掘分析中医药治疗畸形精子症的用药规律[J]. 中国男科学杂志, 2024, 38(1):29-36. doi: 10.3969/j.issn.1008-0848.2024.01.004.
[9]	樊千, 陈赟, 薛建国, 等. 探讨“阳化气、阴成形”理论的聚精汤通过抗氧化应激改善精子线粒体结构和功能治疗弱畸形精子症的临床研究[J]. 中华男科学杂志, 2024, 30(9):813-818. doi: 10.13263/j.cnki.nja.2024.09.007.
[10]	章茂森, 滕凤猛, 安晓飞, 等. 聚精枸橘颗粒对畸形精子症模型大鼠生殖功能干预的实验研究[J]. 中华男科学杂志, 2020, 26(11):1015-1019. doi: 10.13263/j.cnki.nja.2020.11.010.
[11]	张楠, 林铮, 廖海含, 等. 生信分析筛选心衰氧化应激相关关键基因并预测候选药物[J]. 生物信息学, 2024, 22(3):174-182.doi: 10.12113/202302007.
[12]	李鑫茹, 王长健, 王欣跃, 等. 中药数据库的研究进展与应用[J]. 中草药, 2025, 56(1):293-304. doi: 10.7501/j.issn.0253-2670.2025.01.028.
[13]	Platts AE, Dix DJ, Chemes HE, et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs[J]. Hum Mol Genet, 2007, 16(7):763-773. doi: 10.1093/hmg/ddm012. pmid: 17327269
[14]	Ma Y, Guo Y, Yuan G, et al. Triclosan impairs spermatocyte cell proliferation and induces autophagy by regulating microRNA-20a-5 P by pargeting PTEN[J]. Reprod Toxicol, 2024,129:108663. doi: 10.1016/j.reprotox.2024.108663.
[15]	Li R, Xing QW, Wu XL, et al. Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway[J]. Cell Death Dis, 2019, 10(4):307. doi: 10.1038/s41419-019-1547-8. pmid: 30952838
[16]	Wang Y, Kong R, Xie K, et al. Analysis of the Promoter Regions of gga-miR-31 and Its Regulation by RA and C-jun in Chicken[J]. Int J Mol Sci, 2023, 24(15):12516. doi: 10.3390/ijms241512516.
[17]	Chen Y, Xu D, Ma Y, et al. Sertoli cell-derived extracellular vesicles traverse the blood-testis barrier and deliver miR-24-3p inhibitor into germ cells improving sperm mobility[J]. J Control Release, 2023, 362:58-69. doi: 10.1016/j.jconrel.2023.08.031.
[18]	Freitas MJ, Silva JV, Brothag C, et al. Isoform-specific GSK3A activity is negatively correlated with human sperm motility[J]. Mol Hum Reprod, 2019, 25(4):171-183. doi: 10.1093/molehr/gaz009. pmid: 30824926
[19]	Sharif FA, Ashour MJ, Abuwarda HN, et al. Antioxidant Genes Variants and Their Association with Sperm DNA Fragmentation[J]. Biochem Genet, 2024, 62(6):4303-4316. doi: 10.1007/s10528-023-10559-7.
[20]	陈小均, 张志杰, 贾玉森, 等. 畸形精子症获得性病因及治疗研究进展[J]. 中国性科学, 2018, 27(2):107-111. doi: 10.3969/j.issn.1672-1993.2018.02.035.
[21]	任志红, 陆华, 廖超, 等. 五子衍宗丸、定坤丹和康复新液联合治疗畸形精子症疗效观察[J]. 西部中医药, 2020, 33(7):83-85. doi: 10.12174/j.issn.1004-6852.2020.07.21.
[22]	蒋平, 徐青洪, 陈存武, 等. 金匮肾气丸对环磷酰胺所致睾丸损伤小鼠睾丸组织Nrf2信号通路基因表达的影响[J]. 中华男科学杂志, 2020, 26(2):160-166. doi: 10.13263/j.cnki.nja.2020.02.012.
[23]	谢福贤, 翟国敏, 祝俭平. 从瘀论治畸形精子症的临床研究[J]. 齐齐哈尔医学院学报, 2015, 36(16):2362-2363.

排名	CLOSENESS	DEGREE	MNC	MCC
1	PTEN	JUN	JUN	PTEN
2	JUN	PTEN	PTEN	GSK3β
3	GSK3β	GSK3β	GSK3β	HNRNPA1
4	SOD2	NPM1	NPM1	PABPC1
5	SNCA	BRCA1	SOD2	YBX1
6	NPM1	SOD2	BRCA1	G3BP1
7	SDHA	SDHA	TARDBP	HNRNPA2B1
8	PARK7	TARDBP	SNCA	HNRNPD
9	MAPK1	SNCA	SDHA	FUS
10	BRCA1	MAPK1	HNRNPA1	FXR1

排名	CLOSENESS	DEGREE	MNC	MCC
1	PTEN	JUN	JUN	PTEN
2	JUN	PTEN	PTEN	GSK3β
3	GSK3β	GSK3β	GSK3β	HNRNPA1
4	SOD2	NPM1	NPM1	PABPC1
5	SNCA	BRCA1	SOD2	YBX1
6	NPM1	SOD2	BRCA1	G3BP1
7	SDHA	SDHA	TARDBP	HNRNPA2B1
8	PARK7	TARDBP	SNCA	HNRNPD
9	MAPK1	SNCA	SDHA	FUS
10	BRCA1	MAPK1	HNRNPA1	FXR1

序号	基因	中药材
1	SOD2	马齿苋、槟榔、白附子、地黄、苍耳子、山药、板蓝根、白术、山茱萸、桑叶、天冬
2	PTEN	紫苏子、北沙参
3	JUN	半夏、旋覆花、麻黄、钩藤、枳壳、附子
4	GSK3β	薤白、山慈菇、马鞭草、地黄、平贝母、麦冬、苍术、山药、灵芝、大蒜、板蓝根、枸骨叶、北沙参、枸杞子、白芷、浙贝母、人参、土贝母、大青叶、川贝母
5	SDHA	丹参、百部、白附子、山楂、蒲黄、芦荟、苍耳子、牵牛子、片头七、刺五加、两面针、板蓝根、天麻、石草、中节风、蓖麻子、明党参、罗布麻叶、肉苁蓉、党参、苦楝皮、苦参、北沙参、木贼、紫苏叶、银柴胡、半边莲、人参、紫草、紫花地丁、巴戟天、芦根、荆芥、绵萆薢、当归
6	MAPK1	马齿苋、合欢皮

序号	基因	中药材
1	SOD2	马齿苋、槟榔、白附子、地黄、苍耳子、山药、板蓝根、白术、山茱萸、桑叶、天冬
2	PTEN	紫苏子、北沙参
3	JUN	半夏、旋覆花、麻黄、钩藤、枳壳、附子
4	GSK3β	薤白、山慈菇、马鞭草、地黄、平贝母、麦冬、苍术、山药、灵芝、大蒜、板蓝根、枸骨叶、北沙参、枸杞子、白芷、浙贝母、人参、土贝母、大青叶、川贝母
5	SDHA	丹参、百部、白附子、山楂、蒲黄、芦荟、苍耳子、牵牛子、片头七、刺五加、两面针、板蓝根、天麻、石草、中节风、蓖麻子、明党参、罗布麻叶、肉苁蓉、党参、苦楝皮、苦参、北沙参、木贼、紫苏叶、银柴胡、半边莲、人参、紫草、紫花地丁、巴戟天、芦根、荆芥、绵萆薢、当归
6	MAPK1	马齿苋、合欢皮