医药导报2024，Vol.43Issue(5)：667-679,13.DOI:10.3870/j.issn.1004-0781.2024.05.001
天麻素与薯蓣皂苷元配伍对大鼠缺氧损伤脑微血管内皮细胞的保护作用
Protective Effects of Gastrodin and Diosgenin on Hypoxia Injury of Rats Brain Microvascular Endothelial Cells
摘要
Abstract
Objective To investigate the protective effects of gastrodin(Gas),diosgenin(Dio)and their composition(GDC)on the hypoxia injury of rat cerebral microvascular endothelial cells(BMECs),and to study their mechanism of angiogen-esis after cerebral microvascular hypoxia injury.Methods BMECs were divided into five kinds of groups:normal control,model control,Gas groups(1,2,4,8,16,32 μmol·L-1),Dio groups(0.25,0.5,1,2,4,8 μmol·L-1),and GDC groups(the concen-trations of Gas and Dio were 1 and 0.25,2 and 0.5,4 and 1,8 and 2,16 and 4,32 and 8 μmol·L-1,respectively).After 12 hours of treatment,BMECs were subjected to hypoxia-induced by oxygen-glucose deprivation in the control,Gas,Dio,and GDC groups.The LDH leakage rate,IL-1β content,SOD viability,MDA concentration,Hoechst 33258,FITC-Annexin V/PI staining.Transwell chamber assay,scratch wound healing assay,and tube formation assay were employed,and investigated the protective effects of Gas,Dio,and GDC on BMECs in promoting angiogenesis and further using network pharmacology and molecular docking methods to focus on angiogenesis aspects to investigate the mechanism of GDC against cerebral ischemia.Results When Gas and Dio are combined in 2 and 0.5 μmol·L-1,it can significantly increase the cell viability of BMECs(P＜0.05),Promote cell prolifera-tion;Compared with the model control group,LDH leakage rate was decreased in the Gas group(P＜0.05);IL-1β content was de-creased significantly in Gas,Dio,and GDC groups(P＜0.05),SOD vitality was increased in Gas and GDC groups(P＜0.05),Ap-optotic bodies were reduced in the Gas,Dio groups and in the GDC group.GDC can promote proliferation,invasion,migration and tubule formation in the hypoxia model of BMECs,indicating a degree of promoting angiogenesis effect at the cellular level.Network pharmacology found good binding activity between Gas and Caspase-3(CASP3),peroxisome proliferative activated receptor,gam-ma(PPARG),F2,matrix metalloproteinase-9(MMP-9),and serine-threonine kinase(Akt)1,Dio to nitric oxide synthase 3(NOS3)and KDR proteins,and Gas and Dio may regulate angiogenesis after cerebral ischemia mainly through VEGF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway and hypoxia inducible factor-1(HIF-1)signaling pathway.Conclusions Gas,Dio,and GDC have protective effects against hypoxic injury and can promote angiogenesis after hypoxia inju-ry.Their mechanism of action may be related to herb action on Akt 1,NOS 3,VEGFR2 and other proteins,as well as the regulation of signaling pathways such as VEGF/Akt/MAPK to promote angiogenesis.关键词
天麻素/薯蓣皂苷元/脑缺血/脑微血管内皮细胞/血管新生Key words
Gastrodin/Diosgenin/Cerebral ischemia/Brain microvascular endothelial cells/Angiogenesis分类
医药卫生引用本文复制引用
王志昊,祝娜,唐茂红,付饶,阿热依·巴哈提,李彦文,黄秀兰,李志勇..天麻素与薯蓣皂苷元配伍对大鼠缺氧损伤脑微血管内皮细胞的保护作用[J].医药导报,2024,43(5):667-679,13.基金项目
国家自然科学基金面上项目(81473797) （81473797）
中国中医科学院中药研究所中央级公益性科研院所基本科研业务费资助项目(ZXKT23009). （ZXKT23009）
