基于网络药理学对龟甲抗骨质疏松的作用机制研究

目的 运用网络药理学探讨龟甲治疗骨质疏松（osteoporosis，OP）的作用机制。方法 通过中药系统药理学成分分析平台（BATMAN-TCM）数据库及文献获得龟甲活性化合物，再通过TTD、Drugbank 、DisGeNET、OMIM数据库获取OP疾病相关靶点，取二者交集得到龟甲-OP疾病靶点。采用在线分析工具Metascape对龟甲治疗骨质疏松靶基因进行基因本体论（gene ontology，GO）及京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。结果 获得龟甲成分共40个（氨基酸类、脂肪酸类、酯类、甾醇类、其他类），龟甲-OP疾病交集靶点15个（UGT2B17、PTGS2、SLC22A6、SLC22A10、PTGER2、SRC、COMT、TNF 、ESR1、CYP19A1、ESR2、AR、PGR、ITGB3、FPDS）。龟甲活性化合物关键靶点的KEGG富集分析表明其主要与神经活性配体-受体相互作用、氨酰- tRNA生物合成、谷氨酸能突触等信号通路相关。龟甲抗骨质疏松靶基因GO富集分析表明其主要与对类固醇激素的反应、上皮细胞增殖的调控、脂质定位的调节等相关，KEGG通路富集结果解释15个基因主要与类固醇激素生物合成、甲状腺素信号途径、癌症的途径信号通路相关。结论 龟甲治疗OP的作用机制呈多靶点、多途径的特性，不仅影响骨代谢相关途径，还可影响体内多种代谢途径。

Research on the mechanism of anti-osteoporosis of tortoise shell based on the network pharmacology

Objective To explore the mechanism of tortoise shell in the treatment of osteoporosis (OP) using network pharmacology. Methods The tortoise shell active compounds were obtained from the database of BATMAN-TCM and literatures, and then the disease related targets were obtained from the database of TTD, Drugbank, DisGeNET, and OMIM, and the tortoise shell-OP targets were obtained from the intersection of the two.GO and KEGG pathway enrichment analysis was carried out on the target gene of tortoise shell treatment osteoporosis by online analysis tool Metascape.Results 40 compounds (amino acids, fatty acids, esters, sterols, others)of tortoise shell were obtained,and 15 targets (UGT2B17, PTGS2, slc22a6, slc22a10, ptger2, SRC, COMT, TNF, ESR1, CYP19A1, ESR2, AR, PGR, ITGB3, FPDS) were screened out.The analysis of KEGG enrichment of the key target of tortoiseshell active compounds showed that it was mainly related to the signal pathways such as the neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, glutamatergic synapse.The analysis of GO enrichment of tortoise shell anti osteoporosis target gene showed that it was mainly related to the response to steroid hormone, regulation of epithelial cell proliferation, and regulation of lipid location, etc.,and the analysis of KEGG pathway enrichment showed that these genes were mainly related to the steroid hormone biosynthesis, thyroid hormone signaling pathway, pathways in cancer.Conclusion The mechanism of action of tortoise shell in the treatment of OP is multi-target and multi-channel, which not only affects the related pathways of bone metabolism, but also affects many metabolic pathways in vivo.