基于转录组学和网络药理学方法探讨补肾益芪汤治疗 COPD 相关骨质疏松症的作用机制。
Exploring the Mechanisms of Modified Bu-Shen-Yi-Qi Decoction for COPD-Related Osteoporosis Therapy via Transcriptomics and Network Pharmacology Approach.
机构信息
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
出版信息
Drug Des Devel Ther. 2023 Sep 6;17:2727-2745. doi: 10.2147/DDDT.S413532. eCollection 2023.
PURPOSE
To investigate the effectiveness of modified Bu-Shen-Yi-Qi decoction (MBSYQ) in the treatment of osteoporosis associated with chronic obstructive pulmonary disease (COPD) and its underlying mechanisms of action.
METHODS
Disease targets, active ingredients and targets were predicted by TTD, CTD, DisGeNET, HERB (BenCaoZuJian as its Chinese name), and multiple-TCM databases; In addition, the screened targets were performed via the online platforms DAVID 6.8 and Metascape for GO and KEGG pathway enrichment analysis; The relationship between the MBSYQ and core targets were verified by molecular docking technique. Then we established a COPD-associated osteoporosis rat model by passive 24-week cigarette exposure. We assessed the efficacy of MBSYQ by lung histopathology assessment and distal femur/the first lumbar vertebra (L1) microstructural assay. In addition, we performed tibial RNA sequencing, which was validated by RT-PCR and Western blot.
RESULTS
Screening revealed that the 350 active compounds of MBSYQ anchored 228 therapeutic targets for COPD-related osteoporosis; KEGG pathway enrichment analysis showed that the key targets mainly regulated MAPK and PI3K/AKT signaling pathways. In vivo studies showed that MBSYQ treatment alleviated pathological alterations in lung tissue, and reversed the bone loss and microstructure damage in the femur/L1 of model rats. The RNA seq indicated that MBSYQ could upregulate genes associated with anti-oxidative stress and aerobic respiration. The GSEA analysis displayed that MAPK and PI3K/AKT pathways were inhibited by CS exposure and activated by MBSYQ.
CONCLUSION
MBSYQ is effective in the prevention and treatment of COPD-related osteoporosis, partially achieved by improving oxygen metabolism and activating MAPK and PI3K/AKT pathways.
目的
探讨加味补肺益肾汤（MBSYQ）治疗慢性阻塞性肺疾病（COPD）相关骨质疏松症的疗效及其作用机制。
方法
通过 TTD、CTD、DisGeNET、HERB（本草作为中文名）和多个中药数据库预测疾病靶点、活性成分和靶点；此外，通过在线平台 DAVID 6.8 和 Metascape 对筛选出的靶点进行 GO 和 KEGG 通路富集分析；通过分子对接技术验证 MBSYQ 与核心靶点的关系。然后，我们通过被动 24 周吸烟暴露建立了 COPD 相关骨质疏松症大鼠模型。通过肺组织病理学评估和远端股骨/第一腰椎（L1）微结构分析评估 MBSYQ 的疗效。此外，我们进行了胫骨 RNA 测序，并通过 RT-PCR 和 Western blot 进行了验证。
结果
筛选出的 MBSYQ 350 种活性化合物锚定了 228 个 COPD 相关骨质疏松症的治疗靶点；KEGG 通路富集分析表明，关键靶点主要调节 MAPK 和 PI3K/AKT 信号通路。体内研究表明，MBSYQ 治疗可减轻肺组织的病理改变，并逆转模型大鼠股骨/L1 的骨质流失和微结构损伤。RNA seq 表明，MBSYQ 可以上调与抗氧化应激和有氧呼吸相关的基因。GSEA 分析显示，CS 暴露抑制 MAPK 和 PI3K/AKT 通路，而 MBSYQ 激活该通路。
结论
MBSYQ 对 COPD 相关骨质疏松症的防治有效，部分通过改善氧代谢和激活 MAPK 和 PI3K/AKT 通路实现。
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