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1.广州中医药大学 附属深圳市宝安中医院(集团),广东 深圳 518133;
2.北京中医药大学 东直门医院,北京 100700
丁劲,主治医师,从事中医药治疗男性不育症临床及基础研究,E-mail:djdoctor203@163.com
张耀圣,主任医师,教授,硕士生导师,从事中医药防治男科疾病研究,E-mail:ysz3129@163.com
收稿日期:2019-05-30,
网络出版日期:2019-06-18,
纸质出版日期:2019-10-20
移动端阅览
丁劲, 张耀圣, 商建伟. 五子衍宗丸治疗男性不育症的网络药理学探讨[J]. 中国实验方剂学杂志, 2019,25(20):25-35.
Jin DING, Yao-sheng ZHANG, Jian-wei SHANG. Network Pharmacology Research of Wuzi Yanzongwan in Treatment of Male Infertility[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 25-35.
丁劲, 张耀圣, 商建伟. 五子衍宗丸治疗男性不育症的网络药理学探讨[J]. 中国实验方剂学杂志, 2019,25(20):25-35. DOI: 10.13422/j.cnki.syfjx.20191940.
Jin DING, Yao-sheng ZHANG, Jian-wei SHANG. Network Pharmacology Research of Wuzi Yanzongwan in Treatment of Male Infertility[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 25-35. DOI: 10.13422/j.cnki.syfjx.20191940.
目的:
2
基于网络药理学探讨五子衍宗丸治疗男性不育症的物质基础及作用机制。
方法:
2
应用中药系统药理学分析平台(TCMSP) 筛选五子衍宗丸中的活性成分和作用靶点;应用GeneCards,OMIM,PharmGkb数据库筛选男性不育症的疾病靶点;应用R语言软件筛选药物与疾病共同靶点,应用Cytoscape软件构建药物-活性成分-疾病-靶点互作网络;应用STRING平台构建共同靶点蛋白互作网络(PPI);应用ClueGo插件对共同靶点进行基因本体(GO)分析,并应用R语言软件对共同靶点进行京都基因与基因组百科全书(KEGG)通路富集。
结果:
2
从五子衍宗丸中共获得72个有效活性成分,得到35个五子衍宗丸治疗男性不育症的可能靶点,这些靶点主要涉及氧化与抗氧化活性等生物学过程,并主要富集在磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt),缺氧诱导因子-1(HIF-1)等信号通路上。
结论:
2
通过网络药理学证实了五子衍宗丸多成分、多靶点、多途径的作用特点,预测了五子衍宗丸治疗男性不育症的可能作用机制,为进一步研究其活性成分和作用机制提供理论依据。
Objective:
2
Exploring the material basis and mechanism of Wuzi Yanzongwan in the treatment of male infertility based on network pharmacology.
Method:
2
Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active ingredients and targets in Wuzi Yanzongwan. GeneCards
OMIM and PharmGkb databases were used to screen the targets of male infertility. R language software was used to screen common targets of drugs and diseases
Pharmaceutical active ingredients-disease target interaction network was constructed by using Cytoscape software. The common target protein interaction network (PPI) was constructed by STRING platform
the gene ontology(GO) analysis of common target was analyzed by ClueGo plug-in
and Kyoto encyclopedia of genes and genomes(KEGG) pathway was enriched by R language software.
Result:
2
A total of 72 active ingredients were obtained from Wuzi Yanzongwan
and 35 possible targets for the treatment of male infertility were obtained. These targets are mainly involved in biological processes such as oxidation and antioxidant activity
and are mainly concentrated in phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) and hypoxia inducible factor-1(HIF-1) signaling pathways.
Conclusion:
2
The network pharmacology confirmed the multi-component
multi-target and multi-pathway action characteristics of Wuzi Yanzongwan
predicted the possible mechanism of Wuzi Yanzongwan in the treatment of male infertility
and provided theoretical basis for further study of its active ingredients and mechanism.
Jungwirth A , Giwercman A , Tournaye H , et al . European association of urology guidelines on male infertility: the 2012 update [J]. Eur Urol , 2012 , 62 ( 2 ): 324 - 332 .
Barratt C L R , Björndahl L , Tournaye H , et al . The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities [J]. Hum Reprod Update , 2017 , 23 ( 6 ): 660 - 680 .
HUANG C , LI B , XU K , et al . Decline in semen quality among 30, 636 young Chinese men from 2001 to 2015 [J]. Fertil Steril , 2017 , 107 ( 1 ): 83 - 88 .
中华医学会男科分会 . 2016版中国男科疾病诊断治疗指南与专家共识 [M]. 北京 : 人民卫生出版社 , 2017 , 39 - 56 .
ZHOU S H , DENG Y F , LIU Z D , et al . Traditional Chinese medicine as a remedy for male infertility: a review [J]. World J Mens Health , 2019 , doi: 10.5534/wjmh.180069 http://doi.org/10.5534/wjmh.180069 .
王桐生 , 黄金玲 , 吴德玲 , 等 . 五子衍宗丸对少弱精子症模型大鼠精子线粒体膜电位及超微结构影响 [J]. 中华男科学杂志 , 2013 , 19 ( 5 ): 446 - 450 .
张晨曦 , 王永辉 , 许凯霞 , 等 . 不同补益方剂对老龄小鼠生精细胞凋亡的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 8 ): 148 - 153 .
高云霄 , 刘保兴 , 秦茂 , 等 . 五子衍宗丸通过增强支持细胞自噬改善生精功能 [J]. 中华中医药杂志 , 2019 , 34 ( 3 ): 961 - 964 .
张秀平 , 刘保兴 , 秦茂 , 等 . 五子衍宗丸对肾精亏虚证大鼠细胞色素C氧化酶7a2及细胞外信号调节激酶磷酸化水平表达的影响 [J]. 北京中医药大学学报 , 2015 , 38 ( 12 ): 806 - 810 .
高云霄 , 刘保兴 , 秦茂 , 等 . 五子衍宗丸通过增强支持细胞自噬改善生精功能 [J]. 中华中医药杂志 , 2019 , 34 ( 3 ): 961 - 964 .
XU Y P , LIU B X , WANG C H , et al . A Chinese herbal formula, Wuzi Yanzong pill, improves spermatogenesis by modulating the secretory function of Sertoli cells [J]. Chin J Integr Med , 2014 , 20 ( 3 ): 194 - 199 .
HU H X , SUN J , XIE Y L , et al . Effect of modified Wuzi Yanzong Pill on Tip60-mediated apoptosis in testis of male rats after microwave radiation [J]. Chin J Integr Med , 2017 , doi: 10.1007/s11655-017-2425-9 http://doi.org/10.1007/s11655-017-2425-9 .
刘伟 , 周建良 , 陈碧莲 , 等 . HPLC同时测定五子衍宗丸中5种活性成分的含量 [J]. 中国实验方剂学杂志 , 2014 , 20 ( 3 ): 74 - 78 .
LUO T T , LU Y , GUO J , et al . Network pharmacology in research of Chinese medicine formula: methodology, application and prospective [J]. Chin J Integr Med , 2019 , doi: 10.1007/s11655-019-3064-0 http://doi.org/10.1007/s11655-019-3064-0 .
周远 , 苏式兵 . 中药复方配伍的研究方法及其进展 [J]. 中国实验方剂学杂志 , 2019 , doi: 10.13422/j.cnki.syfjx.20191550 http://doi.org/10.13422/j.cnki.syfjx.20191550 .
ZHANG L , LI Q , LIN X , et al . Protective effect of Lycium barbarum polysaccharides against cadmium-induced testicular toxicity in male mice [J]. Food Funct , 2017 , 8 ( 6 ): 2322 - 2330 .
LUO Q , LI J , XING C , et al . The effect of Lycium barbarum polysaccharides on the male rats' reproductive system and spermatogenic cell apoptosis exposed to low-dose ionizing irradiation [J]. J Ethnopharmacol , 2014 , 154 ( 1 ): 249 - 258 .
QIAN L , YU S . Protective effect of polysaccharides from Lycium barbarum on spermatogenesis of mice with impaired reproduction system induced by cyclophosphamide [J]. Am J Reprod Immunol , 2016 , 76 ( 5 ): 383 - 385 .
景晓平 , 崔瑞琴 , 程伟伟 , 等 . 菟丝子黄酮干预雷公藤多苷所致雄性幼鼠生殖损伤 [J]. 中国实验方剂学杂志 , 2016 , 22 ( 10 ): 113 - 117 .
孙晶晶 , 吴秀娟 , 鲍军 , 等 . 菟丝子总黄酮对氢化可的松致大鼠少弱精子症的治疗作用及其机制 [J]. 华西药学杂志 , 2016 , 31 ( 1 ): 14 - 17 .
张宁 , 王素敏 , 车文文 , 等 . 车前子多糖抑制氧化型低密度脂蛋白诱导的血管平滑肌细胞增殖及其机制 [J]. 细胞生物学杂志 , 2009 , 31 ( 5 ): 683 - 688 .
程丹 , 李洁 , 周斌 , 等 . 覆盆子化学成分与药理作用研究进展 [J]. 中药材 , 2012 , 35 ( 11 ): 1873 - 1876 .
刘燕 , 孙红霞 . 五味子多糖的药理学作用研究进展 [J]. 北华大学学报:自然科学版 , 2016 , 17 ( 5 ): 607 - 610 .
Breitbart H , Etkovitz N . Role and regulation of EGFR in actin remodeling in sperm capacitation and the acrosome reaction [J]. Asian J Androl , 2011 , 13 ( 1 ): 106 - 110 .
Rajamanickam G D , Kastelic J P , Thundathil J C . Na/K-ATPase regulates bovine sperm capacitation through raft-and non-raft-mediated signaling mechanisms [J]. Mol Reprod Dev , 2017 , 84 ( 11 ): 1168 - 1182 .
LU N , Sargent K M , Cupp A S , et al . Loss of vascular endothelial growth factor A (VEGFA) isoforms in the testes of male mice causes subfertility, reduces sperm numbers, and alters expression of genes that regulate undifferentiated spermatogonia [J]. Endocrinology , 2013 , 154 ( 12 ): 4790 - 802 .
Sargent K M , Clopton D T , Cupp A S , et al . VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance [J]. Cell Tissue Res , 2016 , 363 ( 1 ): 31 - 45 .
Aitken R J , Clarkson J S , Fishel S . Generation of reactive oxygen species, lipid peroxidation, and human sperm function [J]. Biol Reprod , 1989 , 41 ( 1 ): 183 - 197 .
Aitken R J , Jones K T , Robertson S A . Reactive oxygen species and sperm function in sickness and in health [J]. J Androl , 2012 , 33 ( 6 ): 1096 - 1106 .
Ashok A , Eva T , Rakesh S . Relationship amongst teratozoospermia, seminal oxidative stress and male infertility [J]. Reprod Biol Endocrinol , 2014 , 12 ( 1 ): 45 - 53 .
Nowicka-Bauer K , Lepczynski A , Ozgo M , et al . Sperm mitochondrial dysfunction and oxidative stress as possible reasons for isolated asthenozoospermia [J]. J Physiol Pharmacol , 2018 , doi: 10.26402/jpp.2018.3.05 http://doi.org/10.26402/jpp.2018.3.05 .
YANG J , CHEN L , YANG J , et al . High mobility group box-1 induces migration of vascular smooth muscle cells via TLR4-dependent PI3K/Akt pathway activation [J]. Mol Biol Rep , 2012 , 39 ( 3 ): 3361 - 3367 .
Chambard J C , Leeloch R , Pouysségur J , et al . ERK implication in cell cycle regulation [J]. BBA Mol Cell Research , 2007 , 1773 ( 8 ): 1299 - 1310 .
Schultz M B , Sinclair D A . When stem cells grow old: phenotypes and mechanisms of stem cell aging [J]. Development , 2016 , 143 ( 1 ): 3 - 14 .
Rashid H O , Yadav R K , Kim H R , et al . ER stress: autophagy induction, inhibition and selection [J]. Autophagy , 2015 , 11 ( 11 ): 1956 - 1977 .
Manalo D J , Rowan A , Semenza G L , et al . Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1 [J]. Blood , 2005 , 105 ( 2 ): 659 - 669 .
Kim J W , Tchernyshyov I , DANG C V , et al . HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia [J]. Cell Metab , 2006 , 3 ( 3 ): 177 - 185 .
Volm M , Koomägi R . Hypoxia-inducible factor (HIF-1) and its relationship toapoptosis and proliferation in lung cancer [J]. Anticancer Res , 2000 , 20 ( 3A ): 1527 - 1533 .
WANG G L , JING B H , Semenza G L , et al . Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension [J]. PNAS , 1995 , 92 ( 12 ): 5510 - 5514 .
方坚松 , 刘艾林 , 杜冠华 , 等 . 基于化学信息学方法预测药物靶点的研究进展 [J]. 药学学报 , 2014 , 49 ( 10 ): 1357 - 1364 .
彭利红 , 李泽军 , 陈敏 , 等 . 一种多信息融合的药物-靶标关联预测算法 [J]. 计算机工程 , 2016 , 42 ( 6 ): 218-223,229 .
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