α-氨基苄基磷酸酯类化合物对氧化型低密度脂蛋白或高糖损伤的离体血管内皮细胞的保护作用  

Protective effects of α-aminobenzylphosphonates on endothelial cells injuries induced by ox-LDL or high concentration glucose

作　　者：徐晓庆[1,2] 刘莹[2] 吴宁[2] 杨日芳[2] 胡刚[1] 李锦[2] 

机构地区：[1]南京医科大学药理学系,江苏省神经退行性疾病重点实验室,南京210029 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《国际药学研究杂志》2013年第5期605-610,共6页Journal of International Pharmaceutical Research

摘　　要：目的研究α-氨基苄基膦酸酯类化合物哌芳安他和定哌安他对氧化型低密度脂蛋白或高糖诱导离体人脐静脉内皮细胞损伤的保护作用,并对其可能机制进行研究。方法建立氧化型低密度脂蛋白或高糖诱导的离体人脐静脉内皮细胞损伤模型,通过检测细胞活力变化评价哌芳安他、定哌安他对内皮细胞的保护作用;采用荧光法一氧化氮检测试剂盒检测细胞上清一氧化氮浓度;采用实时定量PCR方法检测细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)及单核细胞趋化因子-1(MCP-1)的mRNA表达水平。结果与正常对照组相比,氧化低密度脂蛋白或高糖处理组细胞活力降低(P<0.05),细胞上清一氧化氮浓度降低(P<0.01),内皮细胞内ICAM-1、VCAM-1和MCP-1的mRNA表达显著上调(P<0.05),或呈上调趋势;与模型组相比,哌芳安他(100和300μmol/L)、定哌安他(10和100μmol/L)处理组细胞活力升高(P<0.05),表现出一定的浓度依赖性,哌芳安他(300μmol/L)及定哌安他(100μmol/L)作用最显著。此外,与模型组相比,哌芳安他(300μmol/L)、定哌安他(100μmol/L)处理组细胞上清一氧化氮浓度升高(P<0.05),内皮细胞内VCAM-1和MCP-1 mRNA表达明显下调(P<0.05),ICAM-1 mRNA表达呈下调的趋势。结论α-氨基苄基磷酸酯类化合物哌芳安他和定哌安他对氧化型低密度脂蛋白或高糖诱导的血管内皮损伤具有保护作用,其机制可能与增加内皮细胞一氧化氮释放及降低细胞黏附分子、趋化因子的表达相关。Objective To investigate the protective effects of α-aminobenzylphosphonates,pivanampeta（PPVP） and dimpiampeta（DMHPPP）,on the injuries of endothelial cells induced by oxidized low density lipoprotein （ox-LDL） or high concentration glucose,and their possible mechanisms.Methods Cellular models of human umbilical vein endothelial cell （HUVEC） injury induced by ox-LDL or high concentration glucose were established.The cell viability was determined to evaluate the protective effects of PPVP and DMHPPP on the injured endothelial cells.The concentration of endothelial cell-released nitric oxide in the medium was tested by fluorometric nitric oxide assay kit,and the mRNA expressions of intercellular cell adhesion molecule-1 （ICAM-1）,vascular cell adhesion molecule-1 （VCAM-1） and monocyte chemotactic protein-1 （MCP-1） were detected by QuantiTect SYBR Green PCR kit.Results Compared with control group,the cell viability of HUVECs induced by ox-LDL or high concentration glucose decreased （P 〈0.05） ; the endothelial cells-released nitric oxide decreased （P 〈0.01） as well; additionally,ICAM-1,VCAM-1 and MCP-1 mRNA expressions were in-regulated significantly.Compared with injured cells groups,PPVP （100 and 300 μmol/L） or DMHPPP （10 and 100 μmol/L） attenuated the decrease in the viability of HUVECs in a concentration-dependent manner （P 〈 0.05）,PPVP （300 μmol/L） or DMHPPP （100 μmol/L） showed the most powerful effects; PPVP （300 μmol/L） or DMHPPP （100 μmol/L） significantly inhibited the reduction of endothelial cell-released nitric oxide （P 〈 0.05） ; in addition,PPVP （300 μmol/l） or DMHPPP （100 μmol/L） significantly down-regulated VCAM-1 and MCP-1 mRNA expressions （P 〈 0.05）,and had a tendency to down-regulate the expression of ICAM-1 mRNA.Conclusion Both PPVP and DMHPPP display protective effects on HUVECs against ox-LDL or high concentration glucose injuries.The mechanisms might be associated with the regulation of the drugs on ni

关 键 词：α-氨基苄基磷酸酯 哌芳安他 定哌安他 动脉粥样硬化 内皮保护 一氧化氮 黏附分子 

分 类 号：R96[医药卫生—药理学]