Akt/eNOS信号途径调节内皮祖细胞存活和功能的实验研究  

oxLDL reduced endothelial progenitor cells survival and function via regulating Akt/eNOS signal pathway

作　　者：马凤霞[1] 任倩[1] 韩忠朝[1] 

机构地区：[1]中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室,天津300020

出　　处：《中华心血管病杂志》2007年第2期173-177,共5页Chinese Journal of Cardiology

摘　　要：目的研究 Akt/eNOS 信号途径是否调节内皮祖细胞(EPC)的存活和功能。方法分离、培养 EPC,然后与不同浓度氧化型低密度脂蛋白(oxLDL)、硝基精氨酸甲酯(L-NAME)或triciribine 孵育48 h,一部分 EPC 与左旋精氨酸预处理后,再与 oxLDL 孵育。然后,检测 EPC 凋亡率及迁移、黏附和管状结构形成能力,同时检测磷酸化 Akt 的蛋白表达、内皮型一氧化氮合酶(eNOS)的蛋白及 mRNA 表达、一氧化氮的产生。结果 oxLDL 剂量依赖性地诱导 EPC 凋亡,抑制 EPC 迁移、黏附及管状结构形成能力,L-NAME 和 triciribine 具有与 oxLDL 相似的作用。oxLDL 的作用能被左旋精氨酸抑制。oxLDL 降低磷酸化 Akt 及 eNOS 蛋白表达,oxLDL 剂量为50μg/ml 时下降率分别为(66±4)%和(68±9)%。而且,oxLDL 降低 EPC eNOS mRNA 的表达及一氧化氮的产生,oxLDL 剂量为50μg/ml 时 eNOS mRNA 表达的下降率为(59±14)%。结论 oxLDL 通过调节 Akt/eNOS 信号途径调节 EPC 的存活和功能。Objective To investigate the association between Akt/eNOS signal pathway changes and the survival/function of endothelial progenitor cells （EPC） in the presence of oxLDL, L-NAME or trieiribine. Methods After 14 d culture, EPC was stimulated with different concentrations of oxLDL, L-NAME or trieiribine for 48 h. In one group, EPC was preineubated with L-arginine for 24 h and then exposed to 50 μg/ml oxLDL for 48 h. The survival and the ability of adhesion, migration and tube structure formation of EPC were observed and the level of phosphorylated Akt protein expression, eNOS protein and mRNA expression were assayed. Results Incubation with oxLDL at concentration 25 μg/ml or higher resulted EPC apoptosis, significantly reduced migratory rate, reduced adhesion to fibroneetin and impaired ability of EPC to form tube structure in a dose-dependent manner. A simultaneous dose-dependent NO generation and Akt phosphorylation decrease as well as eNOS expression reduction at protein and mRNA levels were also observed. Pretreatment of EPC with L-arginine could attenuate these changes. Conclusion oxLDL redueedEPC survival and function via regulating Akt/eNOS signal pathway.

关 键 词：脂蛋白类 LDL 干细胞 一氧化氮合酶 

分 类 号：R543[医药卫生—心血管疾病]