中药新药与临床药理2026，Vol.37Issue(8)：1477-1485,9.DOI:10.19378/j.issn.1003-9783.2026.08.009
白桦脂醇调控 VEGFA/VEGFR2 信号通路抑制 HUVEC 血管新生的作用机制
Mechanism of Betulin Inhibiting Angiogenesis in HUVEC by Regulating the VEGFA/VEGFR2 Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism by which betulin inhibits angiogenesis in human umbilical vein endothelial cell(HUVECs)based on the vascular endothelial growth factor A(VEGFA)/vascular endothelial growth factor receptor 2(VEGFR2)signaling pathway.Methods The effect of different concentrations(0-100 μmol·L-1)of betulin on the proliferation of HUVECs was assessed using the CCK-8 assay,and the appropriate intervention concentrations were selected.Subsequently,HUVECs were divided into a control group,a sorafenib group(5 μmol·L-1),and low-,medium-,and high-dose betulin groups(10,20,30 μmol·L-1).Wound healing assay was used to evaluate cell migration ability;Transwell migration and invasion assays were performed to assess cell migration and invasion capabilities,respectively;tube formation assay was conducted to examine capillary-like structure formation;rat aortic ring sprouting assay and chick chorioallantoic membrane(CAM)assay were employed to evaluate the anti-angiogenic activity of betulin.ELISA was used to measure the secretion level of VEGFA;qRT-PCR was performed to detect the mRNA levels of VEGFA and VEGFR2;Western Blot was carried out to determine the protein expression levels of VEGFA,VEGFR2,AKT,ERK1/2,p-VEGFR2,p-AKT,and p-ERK1/2.Results(1)Betulin at concentrations above 40 μmol·L-1 significantly inhibited HUVEC proliferation(P<0.05),but the cell viability at 40 μmol·L-1 was>85％,indicating a relatively weak effect on proliferation.Therefore,betulin at 10-30 μmol·L-1 was selected for subsequent experiments.(2)Compared with the control group,the low-,medium-,and high-dose betulin groups and the sorafenib group showed significantly reduced cell migration rates in the wound healing assay,as well as reduced migration and invasion rates in Transwell assays(P<0.05,P<0.01).Betulin inhibited HUVEC migration and invasion in a dose-dependent manner(P<0.01).(3)The control group exhibited a large number of three-dimensional tubular structures formed by HUVECs,whereas the betulin groups and the sorafenib group showed markedly fewer tubular structures.The tube formation rate,as well as the microvessel density in rat aortic rings and CAM,were significantly reduced in a dose-dependent manner(P<0.01).(4)Compared with the control group,the low-,medium-,and high-dose betulin groups showed significantly decreased VEGFA secretion levels and VEGFA mRNA expression,as well as significantly reduced protein expression levels of VEGFA,p-VEGFR2/VEGFR2,p-AKT/AKT,and p-ERK1/2/ERK1/2(P<0.05,P<0.01),in a dose-dependent manner(P<0.01).However,no statistically significant difference was observed in VEGFR2 mRNA levels among the groups(P>0.05).Conclusion Betulin may inhibit angiogenesis by modulating the VEGFA/VEGFR2 signaling pathway.关键词
白桦脂醇/人脐静脉内皮细胞/血管新生/VEGFA/VEGFR2 信号通路/作用机制Key words
betulin/human umbilical vein endothelial cells/angiogenesis/VEGFA/VEGFR2 signaling pathway/mechanism of action分类
医药卫生引用本文复制引用
黄曼婷,王耿,李孝虎,卓尚归,吴权辉..白桦脂醇调控 VEGFA/VEGFR2 信号通路抑制 HUVEC 血管新生的作用机制[J].中药新药与临床药理,2026,37(8):1477-1485,9.基金项目
国家自然科学基金项目(82305119) （82305119）
广州中医药大学校院联合科技创新基金项目(GZYZS2024G25,GZYZS2024U20) （GZYZS2024G25,GZYZS2024U20）
国家中医药传承发展示范点项目-中山市中医院中医药科研立项(YN2024A005,YN2024A002) （YN2024A005,YN2024A002）
国家中医药传承发展示范试点项目-院校共建(GZYZS2024XKZ01) （GZYZS2024XKZ01）
中山市中医药传承创新发展科研专项(2024B3015) （2024B3015）
中山市科学技术局项目(2024B1102). （2024B1102）
