氯沙坦对高糖状态下内皮细胞的保护作用及其机制探讨  

Protective effect of losartan on endothelial cells exposed to high glucose levels in vitro

作　　者：李懿萍[1] 汪颖南[2] 邓红[3] 苏宁[1] 

机构地区：[1]东南大学基础医学院病理学系,江苏南京210009 [2]北京海淀区妇幼保健院病理科,北京100080 [3]浙江大学医学院环境基因组中心病理学与病理生理学系,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2006年第3期238-244,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30370658)

摘　　要：目的:探讨高糖环境下氯沙坦对内皮细胞的保护作用及其机制。方法:比色法测定内皮细胞条件培养上清中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性和丙二醛(MDA)水平,RT-PCR方法分析细胞VEGF mRNA的表达水平,EL ISA方法检测细胞分泌的VEGF蛋白。结果:在高糖处理的细胞条件培养上清中SOD和CAT活性降低,而MDA含量升高(P<0.05),同时细胞VEGF mRNA和蛋白质表达增加(P<0.05);而氯沙坦可削弱上述变化,降低内皮细胞MDA含量、增强SOD与CAT活性,以及下调VEGF mRNA和蛋白质表达(P<0.05)。结论:高糖可诱导内皮细胞活性氧产生增多,抗氧化酶活性下降,导致细胞氧化平衡失调,使VEGF mRNA表达与蛋白分泌增加,促进高糖时内皮细胞病变的进展,提示氯沙坦对高糖状态下的内皮细胞的保护作用可能与调节内皮细胞氧化平衡和抑制内皮细胞的活化有关。Objective： To investigate the effect of losartan （an angiotensin Ⅱ type Ⅰ receptor antagonist ） on endothelial cells exposed to high glucose in vitro and related mechanism. Methods： Vascular endothelial cells of human umbilical vein were cultured in media with high glucose levels. The activities of SOD and CAT, the level of MDA were measured by spectrophotometry in the conditioned media of endothelial cells ,the VEGF mRNA expression was performed using semi-quantitative reverse transcription PCR （RT-PCR） in the cell lysates,and the protein expression of VEGF was examined by enzyme-linked immunosorbent assay （ELISA） in the supernatants of cultured cells. Results： When endothelial cells were cultured in high glucose,the activities of SOD and CAT were significantly decreased,but the level of MDA was markedly increased. However, the high glucose-induced effects were inhibited by losartan. The application of high glucose upregulated the mRNA and protein expression of VEGF in endothelial cells, which was also attenuated by losartan. Conclusion： High glucose disrupts the oxidative equilibrium and increases the expression of VEGF in endothelial cells,which can be inhibited by losartan.

关 键 词：血管内皮生长因子/代谢 氯沙坦/药理学 活性氧/代谢 细胞 培养的 血管内皮生长因子/遗传学 RNA 信使/遗传学 碳水化合物 

分 类 号：R965[医药卫生—药理学]