血管紧张素Ⅱ和NADPH氧化酶与血管衰老的相关性研究

Study on the relationship between angiotensinⅡ and NADPH oxidase and vascular aging

目的探讨血管紧张素Ⅱ(AngⅡ)和NADPH氧化酶在血管衰老中的地位及作用机理。方法健康W istar大鼠分为青年组、老龄组、Valsantan组,分析各组大鼠主动脉形态结构及功能;测定血浆和主动脉AngⅡ水平、主动脉活性氧水平;分别应用RT-PCR和W estern bolt检测各组大鼠AngⅡ1型和2型受体(AT1R和AT2R)、NADPH氧化酶p22phox的mRNA及蛋白表达。结果随增龄大鼠主动脉管壁增厚,纤维化程度增高,内皮功能受损,活性氧产生增加;主动脉AngⅡ含量增高,AT2R、p22phox的mRNA及蛋白表达上调,AT1R表达下降;Valsantan(AngⅡ1型受体特异性阻断剂)干预后,p22phox表达下降,活性氧水平降低,衰老血管形态结构和功能异常有所改善。结论衰老血管有其特征性结构和功能改变;AngⅡ经由AT1R上调NADPH氧化酶的基因表达可能是血管衰老的重要机制之一。

Objective To explore the role of angiotensin （Ang） Ⅱ and NADPH oxidase in vascular aging and its action mechanism. Methods The healthy rats were divided into young group, aging group and valsartan group to analyze aorta structure and function, and to detect Ang Ⅱ level in plasma and aorta, and reactive oxygen species （ROS）. RT-PCR and Western blot were used to analyze mRNA and protein expression of NADPH oxidase p22phox, Ang Ⅱ type 1 and 2 receptor （AT1R, AT2R）. Results With aging, aorta wall thickened, fibrosis degree increased, endothelial function were damaged, ROS production enhanced; the level of Ang Ⅱ increased in aorta, mRNA and protein expression of p22phox and AT2R increased, but the expression of AT1 R attenuated. The expression of p22phox and ROS decreased, aorta structural and functional changes were alleviated after treated by valsartan. Conclusions Vascular aging has its specific structure and function changes ; Ang Ⅱ up-regulating the gene expression of NADPH oxidase via AT1R might be one of mechanisms of vascular aging.