基于网络药理学和转录组学分析补血通络丸抗股骨头缺血性坏死的作用机制研究

Study Regarding the Mechanism of Buxue Tongluo Pill Against Osteonecrosis of Femoral Head Based on Network Pharmacology and Transcriptomics

摘要

目的：基于网络药理学和转录组学探讨补血通络丸（Buxue Tongluo pill，BTP）治疗股骨头缺血性坏死(osteonecrosis of femoral head，ONFH)的作用机制。方法：采用大剂量注射地塞米松法复制大鼠ONFH模型。将大鼠分为正常组、模型组、阳性组、补血通络丸低剂量组、补血通络丸中剂量组、补血通络丸高剂量组治疗组，每组6只。连续给药4周后，取股骨头行转录组学测序。结合网络药理学，分析补血通络丸抗ONFH的关键靶点，并对其行基因本体(gene ontology，GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes，KEGG)分析。结果：转录组学测序结果表明，经BTP治疗后，共有308个基因表达量显著变化，其中120个基因上调，188个基因下调。数据集GSE123568以RNA-seq同等参数筛选出178个差异基因，其中143个基因上调，35个基因下调。二者合并后筛选关键靶点出108个。网络药理学结果显示补血通络丸抗ONFH的机制涉及PI3k-Akt信号通路，癌症，细胞周期，泛素介导的蛋白水解等。结论：补血通络丸治疗ONFH是通过多成分、多靶点、多通路来起作用的，主要可能与PI3k-Akt信号通路介导的细胞凋亡有关。

Abstract

Objective: To investigate the preventive mechanism of Buxue Tongluo pill(BTP) against osteonecrosis of femoral head(ONFH) based on network pharmacology and transcriptomics. Methods: We established an ONFH model in SD rats using high dose dexamethasone. Thirty-six rats were randomly divided into six groups, namely normal group, model group, positive group and low-dose group, middle-dose group and high-dose group. Transcriptome sequencing regarding the femoral head was conducted 4 weeks after continuous treatment. Subsequently, mechanism of action of BTP on ONFH determined by integrated network pharmacology. Results: After BTP treatment, 308 genes were significant changed in expression levels, 120 genes being up-regulated and 188 being down-regulated. A total of 108 key targets were targeted for selection. KEGG analysis suggested that various pathways were largely involved in the mechanisms of BTP against ONFH, such as PI3k-Akt signal pathway, cancer, cell cycle and so on. Conclusion: BTP is effective in treating ONFH through multi-components, multi-targets and multi-channels, which may be related to apoptosis mediated by PI3k-Akt signaling pathway.

关键词

补血通络丸 / 转录组学测序 / 网络药理学 / 股骨头缺血性坏死

Key words

Buxue Tongluo pill / transcriptome sequencing / network pharmacology / osteonecrosis of femoral head

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