实用医学杂志2023,Vol.39Issue(24):3175-3181,7.DOI:10.3969/j.issn.1006-5725.2023.24.005
银杏内酯B通过抑制内质网应激拮抗血管内皮损伤的作用机制
Mechanism of ginkgolide B antagonizing vascular endothelial injury by inhibiting endoplasmic reticulum stress
摘要
Abstract
Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).关键词
银杏内酯B/内质网应激/血管内皮损伤/线粒体功能障碍/骨修复Key words
ginkgolide B/endoplasmic reticulum stress/vascular endothelial injury/mitochondrial disorder/bone repair分类
医药卫生引用本文复制引用
马长淞,黄帅,瓦庆德,陈伟之,汪洋,令狐熙涛,唐欲博..银杏内酯B通过抑制内质网应激拮抗血管内皮损伤的作用机制[J].实用医学杂志,2023,39(24):3175-3181,7.基金项目
广东省自然科学基金面上项目(编号:2021A1515011257) (编号:2021A1515011257)
广东省自然科学基金青年提升项目(编号:2023A1515030091) (编号:2023A1515030091)
广东省基础与应用基础研究基金-区域联合基金重点项目(编号:2020B1515120094,2021B1515120053) (编号:2020B1515120094,2021B1515120053)