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

doi:10.3969/j.issn.1006-5725.2023.24.005

Abstract

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 tunicamycin （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）.

Key words: ginkgolide B, endoplasmic reticulum stress, vascular endothelial injury, mitochondrial disorder, bone repair

CLC Number:

R966

Changsong MA,Shuai HUANG,Qingde WA,Weizhi CHEN,Yang WANG,Xitao LINGHU,Yubo. TANG. Mechanism of ginkgolide B antagonizing vascular endothelial injury by inhibiting endoplasmic reticulum stress[J]. The Journal of Practical Medicine, 2023, 39(24): 3175-3181.

Figures/Tables 6

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References 20

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Mechanism of ginkgolide B antagonizing vascular endothelial injury by inhibiting endoplasmic reticulum stress

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