基于网络药理学及分子对接探究肉苁蓉治疗勃起功能障碍的作用机制
杨培1 刘万涛2（通讯作者）

1甘肃医学院基础医学院人体解剖学教研室，甘肃平凉，744000

2甘肃医学院临床医学院外科学教研室，甘肃平凉，74400

摘要：目的：利用网络药理学探究肉苁蓉治疗勃起功能障碍（ED）的作用机制，并通过分子对接验证。方法：通过数据库筛选肉苁蓉的活性成分及作用靶点，并与ED疾病靶点进行比对，获得交集靶点；构建肉苁蓉-活性成分-靶点-ED网络及肉苁蓉-ED蛋白质相互作用网络，进行网络拓扑分析筛选核心活性成分及靶点；运用基因本体功能富集分析和京都基因与基因组百科全书通路富集分析揭示其作用机制；利用分子对接技术验证关键活性成分与核心靶点的结合能力。结果：筛选出肉苁蓉的6种活性成分，并确定327个作用靶点。与ED的3340个疾病靶点比对后，获得182个交集靶点；肉苁蓉-活性成分-靶点-ED网络分析获得肉苁蓉的3种核心活性成分，即苏齐内酯、槲皮素、花生四烯酸，肉苁蓉-ED蛋白质相互作用网络分析获得肉苁蓉治疗ED的核心靶点肿瘤蛋白53（TP53）。京都基因与基因组百科全书通路富集分析分析显示，这些共有靶点主要涉及癌症相关信号通路和磷脂酰肌醇3-激酶/蛋白激酶B信号通路等。分子对接实验结果表明，苏齐内酯与TP53结合能最低，为-7.0kJ/mol，具有较强的结合亲和力。结论：肉苁蓉活性成分苏齐内酯、槲皮素和花生四烯酸可能通过下调TP53的水平来抑制癌症相关信号通路、促进磷脂酰肌醇3-激酶/蛋白激酶B信号通路，进而发挥其抗凋亡、抗炎以及抗氧化作用，减轻阴茎海绵体平滑肌纤维化和内皮损伤，最终改善勃起功能。

关键词：网络药理学；分子对接；肉苁蓉；勃起功能障碍

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