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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。
Objective To investigate the mechanism of losartan in the prevention and treatment of diabetic vascular disease. Methods The effects of losartan at 0.1-1.0 μmol·L -1 on the production of advanced glycation endproducts (AGEs) in vitro were determined by reverse transcription-polymerase chain reaction (RT PCR) and Northern blotting. (HUVECs) on the expression of transforming growth factor (TGF) β1 and fibronectin (FN) in cultured human umbilical vein endothelial cells (HUVECs). Results The expressions of TGFβ1 and FN mRNA in HUVECs treated with AGEs were significantly higher than those in normal controls. Compared with AGEs, the expressions of TGFβ1 and FN mRNA were decreased by 29% and 23%, respectively, in losartan 1.0 μmol·L-1 , Decreased by 50% and 62% at 10 μmol·L-1. Conclusion Losartan can inhibit the formation of extracellular matrix by inhibiting the expression of TGFβ1 and FN mRNA in endothelial cells stimulated by AGEs and prevent vascular remodeling may be one of the mechanisms of prevention and treatment of diabetic vascular complications.