弱氧化低密度脂蛋白对小鼠肠系膜动脉内皮依赖性舒张功能的影响及机制  

Minimally modified LDL induced impairment of endothelium-dependent relaxation in mesenteric arteries of mice

作　　者：陈根[1] 秦旭平[1] 林杰[2] 王俊杰[3] 周楠[4] 李洁[1,2] 

机构地区：[1]南华大学药物药理研究所,湖南衡阳421001 [2]湖南省郴州市第一人民医院,湖南郴州423000 [3]湘南学院,湖南郴州423000 [4]西安交通大学医学院,陕西西安710061

出　　处：《药学学报》2013年第11期1657-1664,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81202535;81173060);湖南省科技厅资助项目(2013FJ3060);湖南省教育厅资助项目(12B117);郴州市科技局资助项目(201216);湘南学院科研基金资助项目(201261)

摘　　要：探讨mmLDL对小鼠肠系膜动脉内皮依赖性舒张功能的影响及机制。采用离体微血管张力描记技术,透射电镜观察血管内皮超微结构。结果显示,mmLDL致小鼠肠系膜动脉内皮细胞明显水肿、内弹力膜断裂;与生理盐水组Rmax(63±5)%和pIC506.42±0.09比较,显著抑制EDHF介导的舒张[Rmax(31±3)%和pIC505.67±0.07,P<0.001,P<0.001];与生理盐水组[Rmax(45±4)%和pIC505.93±0.08]比较,显著抑制NO介导的舒张[Rmax(32±4)%和pIC505.43±0.11,P<0.05,P<0.01];对PGI2介导的舒张功能无明显影响。综上所述,mmLDL损伤内皮细胞超微结构;显著降低内皮依赖性舒张功能与NO-和EDHF途径受损有关。This study is to investigate the impairment and possible mechanism of endothelium-dependent relaxation of mice mesenteric arteries induced by mmLDL. Wire myography was employed to examine endothelial function of mesenteric arteries. Ultramicrostructure of mesenteric vascular beds were detected by transmission electron microscope. The results showed that endothelium cell edema and peeling, vascular elastic membrane fracture traces in mmLDL group. Endothelium-dependent relaxation was decreased in a time- dependent and dose-dependent manner by using mmLDL, compared with normal arteries. In endothelium-derived hyperpolarizing factor （EDHF）-mediated relaxation, the Rmax and plCs0 were decreased from （63 ±5） % and 6.42 ± 0.09 of normal saline control to （31 ±3） % and 5.67±0.07 in mmLDL group （P〈0.001, P〈0.001）, respectively. In nitric oxide （NO）-mediated relaxation, the Rmax and plCs0 were decreased from （45 ±4） % and 5.93 ± 0.08 in normal saline control to （32±4） % and 5.43±0.11 in mmLDL group （P〈0.05, P〈0.01）, respectively. There is no significant alteration of prostacyclin I2 （PGI2） pathway between these two groups. In conclusion, mmLDL induced the impairment of the ultramicrostructure of mesenteric vascular endothelium cell as well as theendothelium-dependent relaxation. The latter includes the dysfunction of NO- and EDHF pathway mediated endothelium-dependent relaxation.

关 键 词：mmLDL 内皮依赖性舒张 一氧化氮 内皮源性超级化因子 肠系膜动脉 

分 类 号：R963[医药卫生—微生物与生化药学]