南方医科大学学报2025，Vol.45Issue(9)：1889-1902,14.DOI:10.12122/j.issn.1673-4254.2025.09.09
金樱子通过调控Src-AKT1轴抑制肺动脉高压平滑肌增殖
Rosa laevigata Michx.inhibits pulmonary arterial smooth muscle cell proliferation in hypertension by modulating the Src-AKT1 axis
摘要
Abstract
Objective To investigate the synergistic mechanism of the traditional Chinese medicine Rosa laevigata Michx.(RLM)for treatment of pulmonary arterial hypertension(PAH).Methods Network pharmacological analysis was carried out to screen the active ingredients of RLM and PAH disease targets and construct the"component-target-disease"interaction network,followed by gene enrichment analysis and molecular docking studies.In the cell experiments,primary cultures of rat pulmonary arterial smooth muscle cells were exposed to hypoxia for 24 h and treated with solvent or 100,200 and 300 mg/mL RLM,and the changes in cell proliferation were detected using Western blotting for PCNA and immunofluorescence staining.In the animal experiment,male SD rats were randomized into 5 control group,monocrotaline(MCT)solvent group,and MCT with RLM(100,200 and 300 mg/mL)treatment groups.HE staining and immunofluorescence staining were used to observe histopathological changes in the pulmonary blood vessels of the rats.Results Seven core active ingredients(including β-sitosterol and kaempferol)in RLM and 39 key disease targets were identified,and molecular docking showed that SRC was a high-affinity target.KEGG enrichment analysis showed that the differential genes were significantly enriched in calcium signaling and PI3K-AKT pathways.In rat pulmonary arterial smooth muscle cells,hypoxic exposure significantly up-regulated cellular expression of PCNA and phosphorylation levels of Src and AKT1,which were obviously lowered by RLM treatment.In RLM-treated rat models,the mean pulmonary artery pressure and right ventricular hypertrophy index(Fulton index)were significantly reduced,the tricuspid annular plane systolic excursion(TAPSE)was improved,and pulmonary vascular wall thickening and fibrosis were obviously ameliorated.Conclusion RLM inhibits pulmonary arterial smooth muscle cell proliferation in rat models of hypertension possibly by regulating the Src-AKT1 axis,suggesting the potential of RLM as a new natural drug for treatment of pulmonary hypertension.关键词
肺动脉高压/平滑肌细胞增殖/AKT1/Src/网络药理学Key words
pulmonary hypertension/smooth muscle cell proliferation/AKT1/Src/network pharmacology引用本文复制引用
杨子为,吕畅,董柱,计书磊,毕生辉,张雪花,王晓武..金樱子通过调控Src-AKT1轴抑制肺动脉高压平滑肌增殖[J].南方医科大学学报,2025,45(9):1889-1902,14.基金项目
国家自然科学基金青年基金(82300470) （82300470）
广东省医学科学技术研究基金项目(B2025246) Supported by Natural Science Foundation for the Youth(NSFY)of China(82300470). （B2025246）
