卡托普利对SHR大鼠eNOS、iNOS表达的影响  

Effect of captopril on expression of eNOS and iNOS in spontaneously hypertensive rats

作　　者：蒋嘉烨 栗源 可燕 JIANG Jiaye;LI Yuan;KE Yan(the Experimental Center for Teaching and Learning,Shanghai University of Traditional Chinese Medicine,Shanghai 201023,China;the Experiment Center of Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai 201203)

机构地区：[1]上海中医药大学教学实验中心,上海201203 [2]上海中医药大学科技实验中心,上海201203

出　　处：《中国比较医学杂志》2022年第3期62-69,共8页Chinese Journal of Comparative Medicine

基　　金：上海中医药大学预算内项目(2021LK031)。

摘　　要：目的 探讨自发性高血压大鼠(spontaneously hypertensive rats, SHR)在高血压发展进程中,卡托普利对SHR内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)和诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)表达的改善作用。方法 以WKY(Wistar-Kyoto)大鼠为空白对照,SHR为模型进行分组实验,7~24周龄SHR灌服卡托普利(3.375 g/(kg·d)),后停药观察至32周龄。测量血压、左室质量指数(left ventricular mass index, LVMI)、主动脉舒张功能、血清亚硝酸根离子(NO;)含量、iNOS、eNOS mRNA以及蛋白含量变化。结果 (1)不同周龄的SHR左室质量指数、血清NO;浓度均高于WKY,主动脉的舒张度均显著低于WKY。(2)mRNA表达含量变化:与WKY相比,不同周龄的SHR的心肌和动脉eNOS和iNOS mRNA表达均较高,其中eNOS/iNOS最大值出现在18周龄;通过灌服卡托普利,在24、32周龄时可显著降低心肌和动脉iNOS和eNOS mRNA的表达。(3)蛋白表达含量变化:与WKY相比,18、24周龄SHR的心肌和动脉iNOS蛋白含量显著升高,24周龄SHR的动脉以及18、24周龄SHR的心肌eNOS蛋白含量显著升高;通过灌服卡托普利,在18、24周龄显著降低动脉iNOS蛋白表达,停药后作用消失;在24和32周龄显著降低心肌iNOS蛋白表达,在32周龄显著降低动脉eNOS蛋白表达和升高心肌eNOS蛋白表达。结论 高血压病理状态可导致iNOS、eNOS的过度表达,而iNOS和eNOS在体内的大量积聚反过来影响高血压的发生;伴随SHR高血压的发病进程,一氧化氮合酶-一氧化氮系统与左室肥厚和内皮功能具有一定的相关性;卡托普利能一定程度上抑制体内iNOS和eNOS的表达,并改善左室肥厚及血管内皮功能。Objective To investigate the effect of captopril on expression of endothelial nitric oxide synthase(eNOS) and inducible nitric oxide synthase(iNOS) in spontaneously hypertensive rats. Methods WKY(Wistar Kyoto) rats were used as the blank control. Spontaneous hypertensive rats(SHR) were used as the model group. SHR aged 7~24 weeks were administered captopril(3.375 g/(kg·d)) and observed at 32 weeks. Blood pressure, left ventricular mass index(LVMI), aortic diastolic function, serum nitrite ion(NO;), and mRNA and protein contents of iNOS and eNOS were measured. Results(1) The left ventricular mass index and serum NO;concentration of SHR were higher than those of WKY rats at various weeks and relaxation of the aorta was significantly lower than in WKY rats.(2) mRNA expression changes: compared with WKY rats, mRNA expression of eNOS and iNOS in the myocardium and arteries of SH rats were higher at various weeks, among which the maximum value of eNOS/iNOS appeared at 18 weeks. After administration of captopril, mRNA expression of iNOS and eNOS in the myocardium and arteries was significantly reduced at 24 and 32 weeks.(3) Protein expression changes: compared with WKY rats, the iNOS protein content in the myocardium and arteries of 18 and 24 weeks SHR were increased significantly, and that of 24 weeks SHR and 18 and 24 weeks SHR was increased significantly. Protein expression of iNOS in arteries was significantly reduced at 18 and 24 weeks by captopril and the effect disappeared after discontinuation. iNOS protein expression was significantly reduced at 24 and 32 weeks. Additionally, at 32 weeks, eNOS protein expression was significantly reduced in arteries and increased in the myocardium. Conclusions The pathological state of hypertension can lead to overexpression of iNOS and eNOS, and accumulation of iNOS and eNOS affects the occurrence of hypertension. Along with the pathogenesis of SHR hypertension, the nitric oxide system has a certain correlation with left ventricular hypertrophy and endothelial function. Capto

关 键 词：自发性高血压 内皮型一氧化氮合酶 诱导型一氧化氮合酶 卡托普利 

分 类 号：R-33[医药卫生]