果糖制备的糖基化终末产物对大鼠离体血管环舒张功能的损伤作用及氯沙坦的保护机制

Protective effects and mechanism of losartan on vasodilation of rat isolated thoratic rings injured by AGEs

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6 d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;10μmol/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 glyeation reaction system from D-fructose was established. The isolated thoracic aortic tings of SD rats were mounted on the organ bath and tension was recorded isometrically. The effect of AGEs on the tings 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 tings were detected by Western blot. The content of NO in aortic tings 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 tings 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 tings 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.