基于网络药理学与转录组学探究白芷抗失重性骨质流失机制  

Mechanism of traditional Chinese medicine Bai Zhi in preventing microgravity induced bone loss based on network pharmacology and transcriptomics

作　　者：梁学超 田野 茹康 桑柏 梁瑞 骞爱荣[1] Liang Xuechao;Tian ye;Ru kang;Sang bo;Liang rui;Qian airong(Xi’an Key Laboratory of Special Medicine and Health Engineering,School of Life Sciences,Northwestern Polytechnical University,Xi’an 710072,China)

机构地区：[1]西安市特种医学与健康工程重点实验室,西北工业大学生命科学学院,西安710072

出　　处：《航天医学与医学工程》2024年第4期228-234,共7页Space Medicine & Medical Engineering

基　　金：国家自然科学基金(32371371);中央高校业务费(D5000230122)。

摘　　要：目的研究白芷对失重性骨质流失的对抗作用及其有效活性成分、作用靶点及分子机制,以期为失重性骨质流失疾病提供新的治疗策略。方法通过构建小鼠后肢尾悬吊力学去负荷模型研究中药白芷对失重性骨质流失的对抗作用。18只健康雄性小鼠随机分为对照组(Control)、尾悬吊组(HLU)和尾悬吊+白芷组(HLU+BZ),每组6只,连续灌胃28 d后,评价白芷对力学去负荷骨质流失模型小鼠骨密度的影响;采用TCMSP、Genecards、OMIM、TTD、DisGeNET等网络药理学数据库筛选出中药白芷有效活性成分及作用靶点;运用转录组测序方法对响应力学去负荷的差异表达基因进行分析,将白芷有效成分作用靶点与响应力学去负荷差异基因靶点交集,获得白芷干预失重性骨质流失的核心基因靶点;利用String数据库和Cytoscape软件构建白芷成分–靶点蛋白互作网络(PPI),采用R Studio软件富集分析白芷治疗失重性骨质流失的关键信号通路。结果对后肢尾悬吊小鼠骨密度扫描定量分析,表明白芷可显著恢复模型小鼠骨密度的损失(P<0.001);通过网络药理学数据库筛选获得10种白芷有效活性成分,306个成分作用靶点,骨质疏松相关疾病靶点1751个,绘制韦恩图计算交集得到33个病药共同靶点。再次通过与模拟失重条件下转录组测序差异表达基因进行靶点交集,获得白芷干预失重性骨质流失的核心基因32个,包括核转录因子(JUN)、Toll样受体4(TLR4)、辣椒素受体(TRPV1)等;对32个核心基因进行富集分析,GO功能富集分析结果显示共得到GO条目194个,其中生物过程(BP)条目123个,主要包括胰岛素样生长因子受体、葡萄糖体内平衡和基因表达负调控等;分子功能(MF)条目28个,包括RNA聚合酶Ⅱ转录因子活性,配体激活的序列特异性DNA结合以及转录因子结合等;细胞组分(CC)条目43个,包括细胞质膜、受体复合物、常染色质等;KEGG富集分析结果Objective In this study,we investigated the active ingredients,targets and molecular mechanisms of Bai zhi based on network pharmacology and mRNA transcriptome sequencing technology for the treatment of microgravity induced bone loss,with a view to providing new therapeutic strategies for microgravity induced bone loss diseases.Methods Investigating the antagonistic effect of the traditional Chinese medicine Bai zhi on microgravity induced bone loss by constructing a hindlimb unloading mice model.18 healthy male mice were randomly divided into Control,HLU and HLU+BZ groups,6 mice in each group,and the effects of Bai zhi on the bone mineral density of the model mice were evaluated after 28 d of continuous gavage.Screening the active ingredients and targets of Bai zhi through TCMSP,Genecards,OMIM,TTD,DisGeNET and other network pharmacology databases.A hindlimb tail suspension unloading animal(HLU)model was established,and the differentially expressed genes(DEGs)responding to mechanical unloading were analyzed using transcriptome sequencing methods,and the targets of Bai zhi active ingredients intersected with the targets of the differentially expressed genes responding to mechanical unloading,so that the core gene targets of Bai zhi for intervening in weightlessness bone loss could be obtained;Construction of Bai zhi component-target protein interaction network(PPI)using String database and Cytoscape software,and enrichment and analysis of key signaling pathways of Bai zhi for treating microgravity induced bone loss using R Studio software.Results Bai zhi effectively restored bone loss in hindlimb tail suspension mice.By quantitative analysis of bone mineral density scanning of hindlimb tail suspension mice,the results showed that Bai zhi significantly restored the loss of bone mineral density in the model mice(P<0.001),Bai zhi has obvious improvement effect on mirogravity induced mice bone loss.10 kinds of Bai zhi effective active ingredients were obtained through the network pharmacology database screening,306 co

关 键 词：失重 骨质流失 转录组测序 白芷 网络药理学 

分 类 号：R856.2[医药卫生—航空、航天与航海医学]