摘要
冠心病的主要病理机制是冠状动脉粥样硬化引起的血管再狭窄，而血管内皮损伤被认为是动脉粥样硬化（atherosclerosis，AS）早期斑块生成的始动因素。大量研究己证明氧化应激与冠状动脉粥样硬化有着密切关系。杨梅苷（myricitrin，五羟基黄酮-3-鼠李糖，Myr）为天然多酚羟基黄酮苷类黄酮化合物，大量存在于杨梅的果实、树皮、树叶和藤茶、蛇葡萄属植物及龙眼叶等其他多种天然植物中，文献报道杨梅苷具有抗氧化、扩张血管作用，并能阻断MAPK／P38信号通路发挥抗炎镇痛的作用，具有较好的防治心血管疾病的潜在开发价值。但是，杨梅苷对血管内皮损伤的保护作用及机制研究尚未见报道。
This study is to report the study of protective effects of myricitrin against oxidative stress-induced apoptosis of vascular endothelial cells and the investigation of the possible mechanisms of action of myricitrin. The model of H2OE-induced apoptosis of vascular endothelial cells was used to determine the protective effects of myricitrin. The levels of LDH, MDA and the activities of SOD, NO were measured using the respective kits. The H2OE-induced apoptosis of vascular endothelial cells was detected using MTT reduction, TUNEL assay, JC-1 and ROS staining. The activation of Caspase-3 was also measured by fluorometry. The expression of apoptosis-related proteins was determined with Western blotting assay. Myricitrin had significant protective effects against HEOE-induced apoptosis of vascular endothelial cells in a time- and dose-dependent manner. The results show that myricitrin could attenuate H2OE-induced decrease in the activities of SOD （P〈0.01）. Myricitrin could decrease the levels of LDH, MDA and increase cell viability and the mitochondrial membrane potential （P〈0.01）. Myricitrin had protective effects in a dose-dependent manner between 32 gmol.L-1 to 64 gmol.L-1. Myricitrin pretreatment could attenuate H2OE-induced increase of p-ERK. Moreover, myricitrin pretreatment could up-regulate the expression of the anti-apoptotic protein Bcl-2, down-regulate the expression of the pro-apoptotic protein Bax, and decrease the expression of Caspase-3, 9. In conclusion, myricitrin had significant protective effects against H2OE-induced apoptosis of vascular endothelial cells. Myricitrin can enhance the activities of anti-oxidative enzymes and decrease the production of free radicals. The possible mechanisms of action of myricitrin are due to myricitrin-mediated inhibition of phosphorylation of the apoptosis signaling pathways-related kinase ERK, up-regulation of the expression of the anti-apoptotic protein, and down-regulation of the expression of the pro-apoptotic protein.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第4期615-620,共6页
Acta Pharmaceutica Sinica
基金
国家"重大新药创制"科技重大专项(2012ZX09103201-004
2012ZX09501001-004)
中央级公益性科研院所基本科研业务专项(yz-12-11)
国家科技支撑计划项目(2008BAI51B02)
