曲美他嗪对内皮祖细胞氧化应激损伤的保护作用研究

Protective effects of trimetazidine on endothelial progenitor cells against oxidative stress injury induced by H_2O_2

目的:研究曲美他嗪(TMZ)对过氧化氢(H2O2)诱导的内皮祖细胞(EPCs)氧化应激损伤的保护作用。方法:采用密度梯度离心法分离人脐带血单个核细胞,使用EBM-2完全培养基诱导单个核细胞向内皮祖细胞分化,经细胞形态学变化及流式细胞术测定内皮祖细胞特异性标记物CD133、CD34和VEGFR抗原来鉴定内皮祖细胞。体外建立内皮祖细胞过氧化氢(100μmol·L^(-1))损伤模型,加入不同浓度曲美他嗪(0.1,0.5,1,5μmol·L^(-1)),观察曲美他嗪作用不同时间后(0.5,1,6,12 h)内皮祖细胞增殖、黏附、迁移、一氧化氮(NO)分泌能力的变化。结果:曲美他嗪呈剂量及时间依赖性降低过氧化氢对内皮祖细胞的氧化应激损伤,保护内皮祖细胞增殖、黏附、迁移、分泌的生物学功能。结论:曲美他嗪在氧化应激条件下对内皮祖细胞生物学功能的保护可能是其心血管保护作用的机制之一。

OBJECTIVE To observe protective effects of trimetazidine（TMZ）on endothelial progenitor cells（EPCs）against oxidative stress injury induced by H2O2.METHODS Umbilical cord blood mononuclear cells were isolated from human umbilical cord blood using density gradient centrifugation,and maintained in an EBM-2 supplemented with EGM-2-MV Single Quots and 5% FBS.EPCs were identified by cell morphology and expression of cell surface antigen CD34,CD133,and VEGFR2.EPCs were treated with or without different concentrations of TMZ for different time periods,and then were exposed to 100μmol·L-1 H2O2 for 2 h to induce oxidative stress.Proliferation,adhesion,migration,and secretion of EPCs in each group were tested.RESULTS TMZ attenuated H2O2-induced injury of EPCs in a concentration-and time-dependent manner,to protect proliferation,adhesion,migration,and secretion of EPCs.CONCLUSION TMZ ameliorates H2O2-induced impairment of biological functions in EPCs,suggesting another mechanism in protection against atherosclerotic diseases.