依普利酮对高盐诱导的高血压大鼠主动脉内皮型一氧化氮合酶表达及活性的影响  

Effects of eplerenone on expression and activity of aortic endothelial nitric oxide synthase in hypertensive rats induced by high-salt intake

作　　者：张倩[1] 丁菁[1] 杨飞[1] 王胜男[1] 粟凤 陆德琴[1] 

机构地区：[1]贵州医科大学病理生理学教研室,贵州贵阳550025

出　　处：《中国病理生理杂志》2015年第9期1606-1610,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30871003);贵州省国际科技合作计划项目[黔科合外G字(2010)7019号]

摘　　要：目的：探讨依普利酮对高盐诱导的高血压大鼠主动脉内皮型一氧化氮合酶（e NOS）的表达及活性的影响。方法：50~60 g 4周龄雄性Wistar大鼠随机分为3组：对照（control,C）组用普通饲料饲养16周,高盐饮食（high salt diet,HS）组及依普利酮（eplerenone,Epl）组用5%高盐饲料饲养16周,C组和HS组于末4周给予同等剂量生理盐水灌胃,而Epl组于末4周给予依普利酮40 mg·kg-1·d-1灌胃。每2周检测各组大鼠尾动脉收缩压,16周后处死大鼠,留取主动脉。ELISA法检测醛固酮含量,蛋白免疫印迹法检测盐皮质激素受体（MR）及e NOS蛋白表达水平,化学比色法测定一氧化氮合酶活性,免疫组化染色法观察主动脉e NOS、神经型一氧化氮合酶（n NOS）及MR蛋白表达与定位。结果：（1）高盐饲料饲养8周后,大鼠收缩压即明显升高,并逐渐上升,16周时HS组收缩压较同时点C组明显升高（P〈0.05）;依普利酮灌胃4周后,收缩压比灌胃前明显下降（P〈0.05）。（2）与C组比较,HS组、Epl组主动脉醛固酮含量明显增加（P〈0.05）,且MR表达明显增加（P〈0.05）。（3）HS组较C组e NOS蛋白表达减少（P〈0.05）、结构型一氧化氮合酶（c NOS）活性也降低（P〈0.05）;Epl组较HS组e NOS蛋白表达增加（P〈0.05）、c NOS活性增高（P〈0.05）。结论：（1）高盐诱导高血压大鼠的主动脉醛固酮含量明显增加,醛固酮可能通过激动MR降低主动脉e NOS蛋白表达及酶活性。（2）选择性MR拮抗剂依普利酮可恢复e NOS蛋白表达及活性,改善e NOS功能。AIM：To explore the effects of eplerenone on the expression and activity of aortic endothelial nitric oxide synthase （ eNOS） in high salt-induced hypertensive rats .METHODS： Male Wistar rats （4 week old, weighting 50~60 g） were randomly divided into control group , high-salt diet group and eplerenone group .The rats in control group were fed with ordinary rodent animal diet , the rats in high-salt group and eplerenone group were exposed to 5%salt diet for 16 weeks and administrated with the same dosage of saline or eplerenone （40 mg？ kg-1？ D-1 ） by gavage for 4 weeks, re-spectively.Systolic blood pressure （SBP） was measured by tail-cuff every 2 weeks.The rats were sacrificed after 16 weeks and the thoracic aorta was collected .The aldosterone content in the aorta was measured by ELISA .The protein levels of mineralocorticoid receptor （MR） and eNOS were determined by Western blot.The activitie of constitutive NOS （cNOS） was measured by chemocolorimetry .The protein localization of eNOS , neuronal nitric oxide synthase （ nNOS） and MR was observed by immunohistochemistry .RESULTS： A process of 8-week high-salt diet increased SBP gradually .SBP in the rats exposure to high salt for 16 weeks was significantly higher than that in control group （ P〈0.05 ） .After 4 weeks of eplerenone treatment, SBP in the rats was significantly lower than that before treatment （P〈0.05）.Compared with control group, the aldosterone content in the aorta were significantly increased in high-salt diet group and eplerenone group （ P〈0.05）, the expression level of MR also increased significantly （P〈0.05）.Compared with control group, both eNOS pro-tein expression （P〈0.05） and cNOS activity in high-salt diet group were significantly decreased （P〈0.05）.The protein＆amp;nbsp;expression of eNOS as well as cNOS activity in aorta increased significantly in eplerenone group compared with high -salt diet group （P〈0.05）. CONCLUSION： Aldosterone content in aorta of high-sal

关 键 词：高血压 高盐饮食 内皮型一氧化氮合酶 盐皮质激素受体 

分 类 号：R363[医药卫生—病理学]