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.

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. DCFHDA 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 tunicamycininduced 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) . [ABSTRACT FROM AUTHOR]