基于系统生物学探讨强骨饮防治原发Ⅰ型骨质疏松症的靶标和作用机制

Study on the mechanism and targets of qiangguyin based on bioinformatics in postmenopausal osteoporosis treatment

目的探讨强骨饮的物质基础及其靶标,阐明强骨饮防治原发Ⅰ型骨质疏松症的多靶点特点和作用机制。方法首先,通过中医药综合数据库(TCMID)、PubChem等数据库确定强骨饮中已知化合物,并用STITCH数据库进行分析。然后,通过中医药分子机制生物信息学分析工具(BATMAN-TCM)预测相关靶标。最后,对靶标进行Gene Ontology(GO)、信号通路和蛋白相互作用网络的富集分析。结果本研究总共纳入强骨饮12味中药相关的435种化合物,2 487个靶标;靶标富集结果显示核酸结合转录因子活性,信号传导活性,氧化还原酶活性等138个GO术语被显著富集(均P<0.05);Wnt信号通路,破骨细胞分化等211个信号通路被显著富集(均P<0.05)。结论将强骨饮中的君臣佐使中药转换为与靶标相互作用的化合物形式,发现强骨饮-化合物-靶标,形成了一个非常复杂的三级网络系统,这种网络关系系统有利于阐明强骨饮的物质基础及强骨饮的配伍机制。靶标功能分析,提示强骨饮靶标和通路不仅直接参与骨重建细胞的分化,成骨、破骨代谢平衡,还通过全身其他系统,如循环系统神经系统等来影响和干预骨微环境。强骨饮治疗原发Ⅰ型骨质疏松症具有多靶点的特点,君臣佐使配伍合理,其作用机制符合目前骨质疏松症疾病的病理机制,其针对骨质疏松症的病因病机,从全身多系统进行干预,协调机体的代谢平衡,具有治病求本的特点。

Objective To investigate the molecular basis of Qiangguyin(QGY) and its predictive targets, to clarify the multi-targets characteristics of QGY in the treatment of Postmenopausal osteoporosis. Methods First, the method of system biology was used to determine the known compounds corresponding to the herbs by the Chinese medicine comprehensive database(TCMID). The name of the compound was determined by NCBI data into the unique ID number. And then we put the data of the unique ID number into the molecular mechanism of the Chinese medicine molecular mechanism bioinformatics analysis tool(BATMAN-TCM) to predict the drug-related gene/protein targets, and then use the bioinformatics method to predict the Gene ontology(GO), signal pathway and protein-protein interaction network of the targets. Results In this study, a total of 435 compounds were included from 12 herbs, and 2 487 targets were retrieved,which were further enriched in 138 GO terms, such as Nucleic Acid Binding Transcription Factor Activity, Signal Transducer Activity, Oxidoreductase Activity(all P<0.05). A total of 211 signal pathways was significantly enriched(all P<0.05). Conclusion The herbs, compounds and targets related to compounds of QGY are effective research carriers for QGY. The prevention and treatment of osteoporosis with QGY is based on multiple target strategies. QGY by coordinating the body’s metabolic balance is preventing and treating osteoporosis for the cause of the disease.