血管紧张素Ⅱ对幼鼠输尿管梗阻后AQP2表达变化的调控  

Angiotensin Ⅱ regulates Aquaporin 2 expression after bilateral ureteral obstruction in rats

作　　者：王焱[1] 文建国[1] 张锐[1] 李真珍[1] 邢璐[1] 王庆伟[1] 张国贤[1] 娄安峰[1] 

机构地区：[1]郑州大学第一附属医院尿动力学中心、泌尿外科和河南省高等学校临床医学重点学科开放实验室,450052

出　　处：《中华小儿外科杂志》2011年第9期696-700,共5页Chinese Journal of Pediatric Surgery

基　　金：河南省医学科技攻关计划资助项目（200801002）本实验在丹麦Aarhus大学临床研究所完成,感谢Frokiaer教授的指导和支持.

摘　　要：目的通过观察血管紧张素Ⅱ（angiotensinⅡ，ANGⅡ）受体阻滞剂坎地沙坦对双侧输尿管梗阻（bilateral ureteral obstruction，BUO）幼鼠肾脏水通道蛋白2（aquaporin 2，AQP2）表达的影响，探讨ANGII对梗阻肾脏功能和AQP2的调控作用。方法24只慕尼黑幼鼠随机分为BUO组、坎地沙坦干预组（BU0＋CAN）和对照组（Sham），每组n=8只。BUO组和BUO＋CAN组均行双侧输尿管结扎，并采用微型泵分别给以生理盐水和坎地沙坦，Sham组仅游离输尿管但不结扎，24h后解除梗阻并继续观察48h后收集血液和肾脏标本，采用免疫印记技术检测肾脏AQP2表达水平。结果梗阻解除后BUO组与Sham组相比尿量显著增高，（92±7）μl·min^-1·kg^-1 比（25±3）μl·min^-1、尿渗透压显著降低，（636±55）mosmol／kgH20比（1853±163）mosmol／kgH2O、血浆渗透压和血浆醛固酮均显著增高，分别为（336±10）mosmol／kgH2O比（303±7）mosmol／kgH2O和（4．1±0．2）nmol／LIL（1．4±0．1）nmol／L；肾脏AQP2表达下调到Sham组17％各组比较差异有统计学意义，P〈0．05。BUO＋CAN组与BUO组相比尿量显著减少，（55±5）μl·min^-1·kg。比（92±7）μl·min^-1·kg^-1，尿渗透压显著增高（783±47）mosmol／kgH2O比（636±55）mosmol／kgH20，血浆醛固酮含量显著降低（2．8±0．5）nmol／L比（4．1±0．2）nmol／L，肾脏AQP2表达增高，各组比较差异有统计学意义，P〈0．05。结论ANGII受体拮抗剂可通过阻止AQP2下调纠正水代谢紊乱，保护肾功能，提示ANGII通过调节肾脏AQP2表达参与输尿管梗阻后肾脏水代谢变化。Objective To investigate the regulation of angiotensin Ⅱ on the expression of Aquaporin 2 （AQP2） and renal function after bilateral ureteral obstruction （BUO）. Methods Tweentyfour Munich-Wistar rats were randomly divided into three groups （BUO,n = 8; CAN n = 8; Sham n = 8）. The BUO （and BUO ＋ CAN） model was built by bilateral ureteral ligation, then the osmotic minipumps contained isotonic saline （n = 8） or candesartan （n = 8） were implanted subcutaneously. Age- and time- matched sham-operated controls （n = 8） were prepared and observed in parallel. The rats were monitored for another 48 h after the 24 h BUO was released. The blood samples were collected and kidneys were harvested to examine the effects of angiotensin II receptor antagonist candesartan on the dysregulation of AQP2 by semi quantitative immunoblottling. Results Release of BUO resulted in a marked polyuria（BUO vs. Sham： 92 ±7 vs. 25 ± 3 μl min^-1 kg 1 , n = 8 ; P〈0. 05） and a reduced urine osmolality（BUO vs. Sham： 636± 55 vs. 1 853 ± 163 mosmol/kgH20,n = 8; P〈0. 05） ,which persisted throughout the experimental period. Administration of candesartan partly prevented this increase in postobstructive urine production （55 ± 5 vs. 92 ± 7 μlmin^-1 kg^-1, n = 8 ; P〈0. 05） and decrease in urine osmolality （783 ±47 vs. 636 ± 55 mosmol kgH2O^-1 ,n = 8; P〈0. 05）. BUO induced a significantly increase in plasma osmolality （336 ± 10 vs. 303 ± 7 mosmol/kgHaO,n = 8; P〈0. 05） and plas-ma aldosterone concentration （4. 1 ± 0. 2 vs. 1.4± 0.1 nmol L^-1, n = 8; P〈0. 05） in BUO vs. in shamoperated control rats. Candesartan partly attenuated the increase of plasma aldosterone （2. 8 ± 0. 5 vs. 4. 1 ± 0. 2 nmol L^-1, n = 8; P〈0. 05）. BUO resulted in a significantly decreased expression of AQP2 compared with control, and candesartan prevented the reduction of AQP2 （P〈0. 05）. Conclusions Angiotensin Ⅱ receptor antagonist prevents dysregulation of AQP2 in response to BUO. Angiot

关 键 词：输尿管梗阻 水通道蛋白质2 血管紧张素Ⅱ受体Ⅰ型拮抗剂 

分 类 号：R726.9[医药卫生—儿科]