氯沙坦对血管紧张素II致培养的牛脑微血管内皮细胞损伤的保护作用  

Protective effect of losartan on bovine cerebral microvessel endothelial cell injury induced by angiotensin II in culture

作　　者：刘慧青[1] 张岫美[1] 魏欣冰[1] 

机构地区：[1]山东大学医学院药理学研究所,山东济南250012

出　　处：《药学学报》2003年第1期5-9,共5页Acta Pharmaceutica Sinica

基　　金：山东省自然科学基金资助项目 (Y95C113 3 )

摘　　要：目的　观察氯沙坦对血管紧张素II(AngII)致牛脑微血管内皮细胞 (BCMECs)损伤的保护作用。方法　用分光光度计测定培养的BCMECs乳酸脱氢酶 (LDH)的漏出量 ,流式细胞仪测定BCMECs细胞间粘附分子 1(ICAM 1)的表达量 ,硝酸还原酶法和放射免疫分析法分别测定BCMECs上清液中一氧化氮 (NO)和内皮素 1(ET1 )的含量。结果　AngII呈剂量依赖性增加BCMECsLDH漏出、NO和ET1 释放及ICAM 1表达 ,氯沙坦对此均有明显抑制作用。结论　氯沙坦抑制AngII致体外培养BCMECs的损伤。Aim To investigate the protective effects of losartan on bovine cerebral microvessel endothelial cell (BCMEC) injury induced by angiotensin II ( Ang II ) in culture. Methods In this study, cultured bovine cerebral microvessel endothelial cells were used and the lactate dehydrogenase (LDH) leakage from bovine cerebral microvessel endothelial cells were observed. Flow cytometry was used to evaluate intercellular adhesion molecule-1 (ICAM-1) expression in bovine cerebral microvessel endothelial cells. Supernatant nitric oxide (NO) and endothelin-1 (ET 1) contents in bovine cerebral microvessel endothelial cells were measured, by NO assay kit and radioimmunoassay, respectively. Results Angiotensin II, in a dose-dependent manner, increased lactate dehydrogenase leakage, NO and ET 1 releases, intercellular adhesion molecule-1 expression of bovine cerebral microvessel endothelial cells. These effects induced by 1×10 -6 mol·L -1 angiotensin II were all significantly inhibited by 1×10 -5 mol·L -1 losartan. Conclusion Angiotensin II may be involved in the initiation and progression of cerebrovascular disease by injuring cerebral endothelium directly and causing endothelial dysfunction. Losartan was shown to protect against angiotensin II-induced bovine cerebral microvessel endothelial cells injury by blocking AT 1 receptor, suggesting that losartan may play a role in the prevention and treatment of cerebrovascular diseases.

关 键 词：脑微血管内皮细胞 血管紧张素Ⅱ 氯沙坦 AT1受体 分光光度计 放射免疫法 硝酸还原酶法 

分 类 号：R965[医药卫生—药理学] R972[医药卫生—药学]