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。

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。