目的 探讨桂枝通络片改善高脂诱导 ApoE-/-小鼠致动脉粥样硬化（AS）伴骨质疏松（OP）的作用机制。 方法 采用质谱分析结合 TCMSP 数据库预测桂枝通络片潜在作用靶点，并通过 DAVID 数据库进行 GO 与 KEGG 富集分析，构建 PPI 网络筛选核心靶点。将 ApoE-/-小鼠随机分为模型组、阿托伐他汀钙片（ATV）组和桂 枝通络片低、高剂量组，高脂喂养 24 周建立动脉粥样硬化合并骨质疏松模型；另取 C57BL/6J 小鼠作为对照 组。采用生化法检测血脂水平；HE 染色观察病理组织学；mirco-CT 观察股骨微结构；ELISA 法检测血清碱性 磷酸酶（BALP）、骨钙素水平；Western Blot 及 qPCR 法检测 PI3K/AKT 通路相关蛋白及 mRNA 表达。MC3T3- E1 细胞分为对照组（成骨分化诱导）、桂枝通络片组（成骨分化诱导+桂枝通络片含药血清）、LY294002 组（成骨分 化诱导+5 µmol·L-1 LY294002）、桂枝通络片+LY294002 组（成骨分化诱导+桂枝通络片含药血清+5 µmol·L-1 LY294002）。采用 CCK-8 法检测细胞增殖率；茜素红染色观察矿化结节；qPCR 法检测 PI3K/AKT 信号通路 相关 mRNA 表达。结果 筛选出桂枝通络片治疗动脉粥样硬化合并骨质疏松潜在靶点基因 408 个，生物信息 学分析提示其作用机制涉及脂质代谢、PI3K-AKT 信号通路。体内实验显示，与模型组比较，桂枝通络片各剂 量组和阿托伐他汀钙片组小鼠血脂水平下降（P＜0.05，P＜0.01）、脂质沉积和肝脂肪变性改善，股骨微结构明 显改善（P＜0.05，P＜0.01）；血清 BALP、骨钙素水平明显升高（P＜0.05，P＜0.0）；骨组织 p-PI3K/PI3K、pAKT/AKT 比值及 PI3k、Akt mRNA 表达明显上调（P＜0.05，P＜0.01）。体外实验显示，桂枝通络片含药血清可 促进 MC3T3-E1 细胞增殖及成骨分化，增强矿化结节形成，并明显上调 PI3k、Akt mRNA 水平（P＜0.01），上 述作用可被 PI3K 抑制剂部分拮抗。结论 桂枝通络片可通过调节脂质代谢、促进成骨分化，在动脉粥样硬化 伴骨质疏松的防治中发挥双重作用，其机制可能与调控 PI3K/AKT 信号通路密切相关。

Objective To investigate the mechanism of action of Guizhi Tongluo Tablets （GZTL） in ameliorating atherosclerosis （AS） with osteoporosis （OP） induced by a high-fat diet in ApoE-/- mice. Methods Mass spectrometry combined with the TCMSP database was used to predict the potential targets of GZTL. GO and KEGG enrichment analyses were performed using the DAVID database， and a PPI network was constructed to screen core targets. ApoE-/- mice were randomly divided into a model group，low- and high-dose GZTL groups，and an atorvastatin calcium （ATV） group. An AS combined with OP model was established by feeding a high-fat diet for 24 weeks. C57BL/6J mice served as the control group. Serum lipid levels were detected by biochemical methods. Histopathology was observed by HE staining. Femoral microstructure was examined by micro-CT. Serum levels of bone alkaline phosphatase （BALP） and osteocalcin were measured by ELISA. Protein and mRNA expression of PI3K/AKT pathway-related molecules were detected by Western Blot and qPCR. MC3T3-E1 cells were divided into a control group （osteogenic differentiation induction）， a GZTL group （osteogenic differentiation induction + GZTL-containing serum）， a LY294002 group （osteogenic differentiation induction + 5 µmol·L-1 LY294002），and a GZTL+LY294002 group （osteogenic differentiation induction + GZTL-containing serum + 5 µmol·L-1 LY294002）. Cell proliferation rate was assessed by CCK-8 assay. Mineralized nodules were observed by Alizarin red staining. mRNA expression related to the PI3K/AKT signaling pathway was detected by qPCR. Results Bioinformatics analysis identified 408 potential target genes of GZTL for treating AS with OP，suggesting mechanisms involving lipid metabolism and the PI3K-AKT signaling pathway. In vivo experiments showed that compared with the model group，mice in the GZTL dose groups and the ATV group exhibited decreased serum lipid levels （P＜0.05， P＜0.01）， improved lipid deposition and hepatic steatosis， significantly improved femoral microstructure （P＜0.05， P＜0.01）， significantly increased serum BALP and osteocalcin levels （P＜0.05，P＜0.01），and significantly upregulated ratios of p-PI3K/PI3K，p-AKT/AKT，and mRNA expression of Pi3k and Akt in bone tissue （P＜0.05，P＜0.01）. In vitro experiments showed that GZTL-containing serum promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells， enhanced the formation of mineralized nodules， and significantly upregulated Pi3k and Akt mRNA levels （P＜0.01）. These effects were partially antagonized by the PI3K inhibitor. Conclusion GZTL exerts a dual effect in the prevention and treatment of AS with OP by regulating lipid metabolism and promoting osteogenic differentiation. Its mechanism is closely related to the regulation of the PI3K/AKT signaling pathway.

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国家自然科学基金项目（82505436，82374406）；广东省医学科学技术研究基金项目（B2025119）；广州市2025年“青年科技人才托举 工程”项目（QT-2025-037）；广州中医药大学“固本”工程一级学科能力提升项目（GZY2025GB0104）；广州中医药大学第一临床医学院2025年 院级“揭榜挂帅”研究生创新能力提升项目（A3-0317-25-110-002）；2025年度大学生创新创业训练计划项目（202510572025）。