晚期糖基化终产物通过肾素-血管紧张素系统上调内皮细胞血管生成样蛋白-4的表达  

Advanced Glycation End Products Upregulate the Expression of Angiopoietin-like Protein 4 Via Activation the Renin-angiotensin System in Endothelials

作　　者：成彩联[1] 郑振达[2] 刘迅[1] 汤颖[3] 叶增纯[1] 娄探奇[1] 

机构地区：[1]中山大学附属第三医院肾内科,广州510630 [2]中山大学附属第三医院心内科,广州510630 [3]中山大学附属第二医院肾内科,广州510120

出　　处：《中山大学学报（医学科学版）》2013年第2期188-192,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家科技支撑计划(2011BAI10B05);广东省科技计划项目(2011B080701005;2010B031600202);广东省医学科研基金(A2010164)

摘　　要：【目的】观察晚期糖基化终产物对内皮细胞血管生成样蛋白-4表达的影响及作用机制。【方法】不同浓度晚期糖基化终产物(AGE)干预内皮细胞24 h,实时荧光定量PCR和免疫印迹检测血管生成样蛋白-4 mRNA和蛋白的表达,酶联免疫吸附试验法(ELISA)检测细胞上清和裂解液中血管紧张素Ⅱ的浓度,异硫氰酸荧光素标记的葡聚糖漏出率和跨内皮电阻检测内皮细胞的通透性。预氯沙坦(10-5mol/L)预处理内皮细胞后,观察Angptl-4和内皮细胞通透性的变化。【结果】AGE上调内皮细胞血管生成样蛋白-4的mRNA和蛋白的表达(P<0.05),升高细胞上清及裂解液中血管紧张素Ⅱ的水平,增加内皮细胞的通透性(P<0.05),氯沙坦预处理后能减轻AGE介导的这些改变(P<0.05)。【结论】AGE可能通过激活内皮细胞内的肾素-血管紧张素系统,上调血管生成样蛋白-4表达的机制,增加内皮细胞的通透性。[ Objective ] To investigate the effects of advanced glycation end products （AGE） on the expression of angiopoietin- like protein 4 and its mechanisms. [ Methods ] Endothelial cells were incubated with various concentrations of AGE for 24 hours, the expression of angiopoietin-like protein 4 were detected by real-time PCR and Western blot analysis, the concentration of angiotensin Ⅱ in conditioned media and cell lysates were measured by enzyme-linked immunosorbent assay, FITC-labeled dextran filtration assay and transendothelial electrical resistance were performed to evaluate endothelial permeability. [ Results ] AGE increased the expression of angiopoietin-like protein g parallel with an increase in the levels of angiotensin Ⅱ （P 〈 0.05）. Incubation with AGE also resulted in a significant increase in endothelial permeability （P 〈 0.05）. However, pretreatment with angiotensin Ⅱ receptor blocker Losartan （ 10^-5 mol/L） blunted these effects induced by AGE （P 〈 0.05）. [Conclusions] AGE upregulated the expression of angiopoietin-like protein 4 via activation local renin-angiotensin system in endothelial cells, which may be a new mechanism for AGEs increasing endothelial permeability.

关 键 词：晚期糖基化终产物 内皮细胞 肾素-血管紧张素系统 血管生成样蛋白-4 

分 类 号：R587[医药卫生—内分泌]