银杏叶提取物(EGb761)在临床上被广泛用于减轻心肌缺血再灌注损伤(MIRI)。微血管内皮细胞(MVECs)可能是体外针对MIRI的作用和机制研究的合适细胞模型。然而,EGb761对MVECs抗缺氧/复氧(H/R)损伤的保护作用鲜有报道。在这项研究中,用EGb761处理H/R损伤的MVECs,然后检测细胞活力,凋亡,ROS生产,SOD活性,caspase-3活性,和ATM的蛋白质水平,γ-H2AX,测量p53和Bax。转染ATMsiRNA以研究ATM途径中蛋白质的变化。EGb761对H/R损伤的MVECs具有保护作用,随着细胞死亡的减少,凋亡,ROS,SOD活性升高。接下来,EGb761可以抑制H/R诱导的ATM,γ-H2AX,p53和Bax呈剂量依赖性。此外,ATMsiRNA还可以抑制H/R诱导的ATM,γ-H2AX,p53和Bax总的来说,这些发现验证了EGB761保护心脏MVECs免受H/R损伤,第一次,说明EGb761通过抑制ROS对ATM途径和细胞凋亡的影响。
Ginkgo biloba extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.