培哚普利对慢性心力衰竭大鼠肾脏水通道蛋白2的影响

Effects of perindoprfl on expression of kidney aquaporin-2 and urine aquaporin-2 excretion in chronic heart failure rats

目的探讨慢性心力衰竭（心衰）大鼠肾脏水通道蛋白2（aquapofin-2，AQP2）表达和尿液AQP2浓度的变化，及培哚普利对其的影响。方法雄性sD大鼠60只，按照简单随机化分组法分为对照组、生理盐水组和培哚普利组，每组20只。建立大鼠心衰模型，生理盐水组、培哚普利组大鼠左心室梗死面积（left ventricular myocardial infarction size, LVMI）≥20％者选人各自心衰亚组，LVMI〈20％者选入各自心功能代偿亚组。干预后检测大鼠血压、血钠浓度、尿量以及尿渗透压，免疫组织化学、逆转录-聚合酶链反应（RT—PCR）、蛋白质印迹法（Westernblot）法检测大鼠肾脏AQP2mRNA和蛋白的表达情况，放射免疫法检测血浆血管加压素（argininevasopressin，AVP）的浓度，间接ELISA法检测尿液AQP2的浓度。结果生理盐水组心衰亚组大鼠肾脏组织AQP2表达、mRNA和蛋白的相对表达量（分别为0．2013±0．0417、0．98±0．33和0．94±0．21，n=13）均显著高于对照组（分别为0．1518±0．0214、0．58±0．51和0．51±0．46，n=20）（P均〈0．05），而培哚普利组心衰亚组大鼠（分别为0．0712±0．0218、0．76±0．45和0．82±0．49，n=13）均显著低于生理盐水组心衰亚组，但仍高于对照组（P均〈0．05）。生理盐水组心衰亚组大鼠血浆AVP浓度、尿液AQP2浓度[分别为（82．52±11．77）ng／L、（19．72±3．91）ng／ml，n=13]均显著高于对照组[分别为（51．67±12．58）ne／L、（6．94±3．10）ng／ml，n=20]（P均〈0．05），培哚普利组心衰亚组大鼠[分别为（15．65±4．10）ng／L、（71．65±9．21）ng／ml，n=13]均显著低于生理盐水组心衰亚组，但仍显著高于对照组（P均〈0．05）。结论慢性心力衰竭大鼠肾脏AQP2表达水平及尿液AQP2排泄均升高，而培哚普利可下调AQP2的表达水平、减少尿液AQP2排泄。

Objective To determine the expression of kidney aquaporin-2 （AQP2） and urine AQP2 excretion in chronic heart failure （CHF） rats and investigate effects of perindoprll on the expression and excretion of AQP2. Methods Sixty rats were randomized into three groups： control group, CHF group, CHF ＋ Perindopril group. According to left ventricular myocardial infarction size, CHF group and perindopril group were further divided into heart failure subgroup （LVMI I〉20% ）and cardiac functional compensation subgroup（ LVMI 〈 20% ） , respectively. Blood and urine samples were collected from the rats for measuring serum Na ＋ , urine volume and urine osmolality. The concentration of plasma arginine vasopressin （p-AVP） was detected by radioimmunoassay （RIA）. Immunohistochemistry, semi-quantitative real time-polymerase chain reaction （RT-PCR） and Western blot were performed for measurement of kidney inner medullary AQP2. The concentration of Urine AQP2 was measured by indirect enzyme-linked immunosorbent assay （indirect ELISA）. Results Immunohistochemistry, RT-PCR, Western blot examinations revealed increased quantity of the inner kidney medullary AQP2 expression （0. 2013 ±0. 0417）, AQP2 mRNA （0. 98 ±0. 33） and AQP2 protein expression（0.94±0. 21 ） in heart failure subgroup（ n = 13 ） compared to control group （ n = 20,0. 1518±0. 0214,0. 58± 0. 51,0. 51± 0.46 ）, which could be significantly by perindopril（ n = 13, 0. 0712±0. 0218,0.76 ±0.45,0. 82 ＋0. 49, all P 〈0.05 vs. heart failure subgroup）. The concentration of plasma arginine AVP[ （ 19.72 ± 3.91 ） ng/ml] and Urine AQP2[ （82. 52± 11.77） ng/L] were significantly higher in heart failure subgroup than in control group [ n = 20, （ 51.67 ± 12. 58 ） ng/L, （ 6.94 ± 3.10）ng/ml] （P 〈 0. 05 ） , which were significantly reduced by perindopril [ n = 13, （ 15.65±4. 10） ng/L, （71.65±9. 21 ） ng/ml ]. Conclusion Increased expression of the kidney inner medullary AQP2 and the excretion of urine AQP2 in chronic heart failure rats could be reduced by perindopril.