中药新药与临床药理2026，Vol.37Issue(3)：424-436,13.DOI:10.19378/j.issn.1003-9783.2026.03.005
桂枝通络片改善高脂诱导的ApoE-/-小鼠动脉粥样硬化伴骨质疏松的作用机制
Mechanistic Study on Guizhi Tongluo Tablets Ameliorating Atherosclerosis with Osteoporosis in High-Fat Diet-Fed ApoE-/-Mice
摘要
Abstract
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.关键词
桂枝通络片/动脉粥样硬化/骨质疏松/质谱分析/网络药理学/脂质代谢/PI3K/AKT通路/MC3T3-E1/ApoE-/-小鼠Key words
Guizhi Tongluo Tablets/atherosclerosis/osteoporosis/mass spectrometry/network pharmacology/lipid metabolism/PI3K/AKT pathway/MC3T3-E1/ApoE-/-mice分类
医药卫生引用本文复制引用
何星灵,张诗茵,萧博迪,妮尕热·艾合买提,鲁路,倪世豪,张一慧,李思静,张小娇,李心雨,陈嘉慧,李姿儒,陈星伶,李嘉祺..桂枝通络片改善高脂诱导的ApoE-/-小鼠动脉粥样硬化伴骨质疏松的作用机制[J].中药新药与临床药理,2026,37(3):424-436,13.基金项目
国家自然科学基金项目(82505436,82374406) （82505436,82374406）
广东省医学科学技术研究基金项目(B2025119) （B2025119）
广州市2025年"青年科技人才托举工程"项目(QT-2025-037) （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) （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) （A3-0317-25-110-002）
2025年度大学生创新创业训练计划项目(202510572025). （202510572025）
