摘要
目的观察奈必洛尔对非对称性二甲基精氨酸(ADMA)诱导损伤人脐静脉内皮细胞(HUVECs)的保护作用。方法用ADMA16μmol/L培养HUVECs 24 h,不加或加入阿替洛尔20μmol/L、奈比洛尔(5μmol/L、10μmol/L、20μmol/L)预处理1 h。0.25%胰酶消化细胞,获取细胞悬液,离心收集细胞上清液,检测一氧化氮(NO)水平、一氧化氮合酶(NOS)活性。提取HUVECs总RNA,用RT-PCR分析内皮型一氧化氮合酶(eNOS)mRNA表达。结果 ADMA16μmol/L刺激HUVECs 24 h后,上清液NO含量和NOS活性降低,eNOS mRNA表达下调。奈比洛尔可剂量依赖性抑制ADMA所致的上述损伤。阿替洛尔对ADMA诱导的损伤无显著改善。结论奈必洛尔可保护ADMA诱导损伤HUVECs。
Objective To investigate the protective effect of nebivolol on asymmetrical dimethylarginine(ADMA)-induced injury of human umbilical vein endothelial cells(HUVECs).Methods HUVECs were cultured with ADMA 16 μmol/L for 24 hours in the absence or presence of nebivolol(5 μmol/L,10 μmol/L or 20 μmol/L)or atenolol(20 μmol/L)for 1 hour.The supernaent in the conditioned medium was collected by centrifugation for determination of nitric oxide(NO)and nitric oxide synthase(NOS)activities.The expression of endothelial nitric oxide synthase(eNOS)mRNA was measured by real time polymerase chain reaction(RT-PCR).Results After the culture of HUVECs with ADMA 16 μmol/L for 24 hours,the NO content and NOS activity in the supernatant decreased,and the expression of eNOS mRNA was down-regulated.Pretreatment with nebivolol concentration-dependently attenuated the ADMA-induced injury.Atenolol had no influence on the effects induced by ADMA.Conclusion Nebivolol protects the ADMA-induced injury of HUVECs
引文
[1]呼晓雷,周继朋,陈小平.AGXT2与ADMA代谢及心脑血管疾病的研究进展[J].中国药理学通报,2015,31(5):601-605.
[2]Wang Y,Zhang M,Liu Y,et al.The effect of nebivolol on asymmetric dimethylarginine system in spontaneously hypertension rats[J].Vascul Pharmacol,2011,54(1/2):36-43.
[3]郭维康,刁宗礼,刘文虎.ADMA通过引起脐静脉内皮细胞内质网应激而诱导细胞凋亡[J].临床和实验医学杂志,2016,15(3):201-203.
[4]姚瑞,党瑜华,张菲斐.非对称性二甲基精氨酸对人脐静脉内皮细胞功能的影响[J].中国动脉硬化杂志,2005,13(4):471-474.
[5]王燕,张明升,刘宇,等.奈比洛尔对自发性高血压大鼠主动脉血管反应性的影响[J].中西医结合心脑血管病杂志,2010,8(10):1204-1206.
[6]Wang Y,Dong X.Nebivolol ameliorates asymmetric dimethylarginine-induced vascular response in rat aorta viaβ3adrenoceptor-mediated mechanism[J].Clin Exp Hypertens,2016,38(2):252-259.