氯沙坦抑制糖基化终末产物刺激培养的人内皮细胞外基质基因的表达  

Losartan inhibits the expression of extracellular matrix mRNA stimulated by advanced glycation end products in cultured human vascular endothelial cells

作　　者：郑丽丽[1] 李承光[2] 朱琳[2] 傅向华[1] 叶启霞[2] 王筠[2] 范清堂[2] 

机构地区：[1]河北医科大学第二附属医院心内科,河北石家庄050017 [2]河南医科大学,河南郑州450052

出　　处：《中国药理学与毒理学杂志》2002年第2期120-123,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的　探讨氯沙坦防治糖尿病血管病变的作用机理。方法　用反转录 聚合酶链反应 (RT PCR)和Northern印迹杂交方法测定了 0 .1～ 10 μmol·L- 1浓度的氯沙坦对经体外制备的糖基化终末代谢产物(AGEs)处理培养的人脐静脉内皮细胞 (HUVECs)转化生长因子 (TGF) β1和纤连蛋白 (FN)基因表达的影响。结果　由AGEs处理的HUVECsTGF β1和FNmRNA表达较正常对照组明显增高 ;与AGEs组相比 ,TGF β1和FNmRNA的表达在氯沙坦 1.0 μmol·L- 1时分别降低了 2 9%和 2 3%,10 μmol·L- 1时降低了 5 6 %和 6 2 %。结论　氯沙坦通过抑制AGEs刺激的内皮细胞TGF β1和FNmRNA表达 ,从而抑制细胞外基质的生成 ,防止血管重构可能是其防治糖尿病血管并发病的机理之一。AIM To investigate the mechanism of preventive and therapeutic actions of losartan on diabetic angiopathy. METHODS Reverse transcription-polymerase chain reaction(RT-PCR) and Northern blot were applied to determine the effect of losartan over the concentration range from 0.1 to 10 μmol·L -1 on inhibiting both gene expression of transforming growth factor(TGF)-β 1 and fibronectin (FN) that were stimulated by advanced glycation end products(AGEs) in cultured human umbilical vein endothelial cells(HUVECs). RESULTS The expression of TGF-β 1 and FN mRNA was higher in the HUVECs stimulated by AGEs than control groups of the cells. Administration of losartan suppressed the expression of TGF-β 1 and FN mRNA by 29% and 23% at 1.0 μmol·L -1 , 56% and 62% at 10 μmol·L -1 . CONCLUSION Losartan can reduce the forming of extracellular matrix by decreasing the expression of TGF-β 1 and FN mRNA, which maybe one possible mechanism of losartan to prevent diabetic angiopathy.

关 键 词：糖基化终末产物 内皮细胞 转化生长因子Β 氯沙坦 细胞外基质 糖尿病 

分 类 号：R966[医药卫生—药理学]