目的 观察果糖制备的糖基化终末产物对大鼠离体血管环内皮依赖性舒张反应的损伤以及氯沙坦的保护作用和机制.方法 用果糖和牛血清白蛋白(BSA)共同孵育制备AGEs；用离体血管环灌流的方法,观察不同浓度氯沙坦对AGEs引起的血管内皮依赖性舒张反应的保护作用；检测血管环中eNOS和AKT的磷酸化表达及NO含量.结果 果糖和BSA共同孵育6d后可得到AGEs,且AGEs可引起血管环对乙酰胆碱诱导的舒张反应下降；10 μmol/L和50μmol/L的氯沙坦均可改善内皮依赖的舒张反应.AGEs还明显降低血管环中NO含量和eNOS及AKT磷酸化水平,氯沙坦可恢复上述指标.结论 果糖制备的AGEs能降低血管环内皮依赖性舒张反应,而氯沙坦则具有保护作用,其机制与阻断血管内皮细胞AT1受体、活化AKT激酶而改善内皮eNOS活性和降低NO生成有关.%Objective To investigate the effects and mechanisms of losartan on endothelium-dependent relaxation injured by AGEs made from D-fructose. Methods The non-enzymatic glycation reaction system from D-fructose was established. The isolated thoracic aortic rings of SD rats were mounted on the organ bath and tension was recorded isometrically. The effect of AGEs on the rings with endothelium intact precontracted by the phenylephrine (PE, 1μmol/L) , and the effect of losartan on the vessel reaction injured by AGEs were recorded with biological signal analytical system. The expressions of phospho-eNOS and phospho-AKT in aortic rings were detected by Western blot. The content of NO in aortic rings was also analyzed. Results AGEs was formatted after 6 days. AGEs inhibited vasodilation induced by Ach. Losartan (50 μmol/L) improved the relaxation to the Ach. The content of NO in aortic rings incubated with AGEs for 1 h was decreased and losartan improved NO production. Losartan also improved the expressions of phosphor-eNOS and phospho-AKT in aortic rings incubated with AGEs. Conclusions D-fructose could induce AGEs formation within 6 days and the AGEs could injure endothelium-dependent relaxation of rat aortic rings. Losartan could reduced NO production induced by AGEs and improve the eNOS and AKT activities.
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