补肾阳中药治疗促性腺激素缺乏型男性不育的网络分子机制初探

Preliminary study on the molecular mechanism of tonifying kidney-yang Chinese medicine in treating gonadotropin-deficient male infertility

目的初探补肾阳中药治疗促性腺激素缺乏型男性不育的潜在分子机制。方法结合生物信息学方法建立补肾阳中药的成分库、表征美国食品药品监督管理局(Food and Drug Administration,FDA)批准用于治疗促性腺激素缺乏男性不育的药物靶标库;再应用通路分析软件(ingenuity pathway analysis,IPA)将成分库投影靶标库,筛选出可作用于靶标及通路的成分,预测分子成分功能,构建“成分-靶标”分子网络。结果分别建立了补肾阳中药成分库(242个化合物)与FDA批准药物靶标库(565个靶标),成分库与靶标库投影后发现补肾阳中药成分库中的30个化学成分可直接激活或抑制药物靶标库中的60个靶标,参与缺氧诱导因子1-α(hypoxia-inducible factor 1-alpha,HIF1α)信号途径,血小板反应蛋白1(thrombospondin 1,TSP1)抑制血管生成途径,芳基烃受体信号途径,孕烷X受体(pregnane X receptor,PXR)/类视黄醇X受体(retinoid X receptor,RXR)激活等18条通路的直接调控。结论本研究构建了补肾阳中药治疗促性腺激素缺乏型男性不育的“成分-靶标”分子网络,分析其治疗效应机制,为补肾阳中药治疗促性腺激素缺乏型男性不育奠定理论基础和实验依据,具有一定的科学意义。

Objective To explore the potential molecular mechanism of tonifying kidney-yang by herbal medicine in treatment of gonadotropin-deficient male infertility.Methods Bioinformatics method was used to establish the library of the composition of herbal medicine in tonifiying kidney-yang,and the library of the drug targets approved by FDA in treating gonadotropin-deficient male infertility.IPA is used to project the ingredient library into the target library.then the researchers selected the compounds that acted on the targets and pathways,predicted the functions of the compounds,and constructed a“component-target”molecular network.Results The tonifying kidney-yang ingredient library(242 compounds)and the FDA-approved drug target library(565 targets)were established.After the component library and target library were projected,it was found that 30 chemical components in the tonifying kidney-yang ingredient library can be directly activated or inhibited 60 targets in the drug target library,and directly regulate 18 pathways in HIF1αsignaling,inhibition of angiogenesis by TSP1,aryl hydrocarbon receptor signaling,PXR/RXR activation.Conclusion This study constructed a molecular network of“component-target”for the treatment of gonadotropin-deficient male infertility by tonifying kidney-yang with herbal medicine,and revealed the signal transduction mechanism of therapeutic effects.This study lays a theoretical foundation and experimental basis for tonifying kidney-yang by herbal medicine against gonadotropin-deficient male infertility.