CAJ | 학술논문

目的通过观察血管紧张素Ⅱ(angiotensin Ⅱ，ANG Ⅱ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ANG Ⅱ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(BUO+ 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·kg-1、尿渗透压显著降低，(636±55) mosmol/kgH2O比(1 853±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/L比(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-1比(92±7)μl·min-1 ·kg-1，尿渗透压显著增高(783±47) mosmol/kgH2O比(636±55) mosmol/kgH2O，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 ANG Ⅱ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ANG Ⅱ通过调节肾脏AQP2表达参与输尿管梗阻后肾脏水代谢变化。
목적 통과관찰혈관긴장소Ⅱ(angiotensin Ⅱ，ANG Ⅱ수체조체제감지사탄대쌍측수뇨관경조(bilateral ureteral obstruction，BUO)유서신장수통도단백2(aquaporin 2，AQP2)표체적영향，탐토ANG Ⅱ대경조신장공능화AQP2적조공작용。방법 24지모니흑유서수궤분위BUO조、감지사탄간예조(BUO+ CAN)화대조조(Sham)，매조n=8지。BUO조화BUO+ CAN조균행쌍측수뇨관결찰，병채용미형빙분별급이생리염수화감지사탄，Sham조부유리수뇨관단불결찰，24h후해제경조병계속관찰48h후수집혈액화신장표본，채용면역인기기술검측신장AQP2표체수평。결과 경조해제후BUO조여Sham조상비뇨량현저증고，(92±7)μl·min-1 ·kg-1비(25±3)μl· min-1·kg-1、뇨삼투압현저강저，(636±55) mosmol/kgH2O비(1 853±163) mosmol/kgH2O、혈장삼투압화혈장철고동균현저증고，분별위(336±10) mosmol/kgH2O비(303±7)mosmol/kgH2O화(4.1±0.2)nmol/L비(1.4±0.1)nmol/L;신장AQP2표체하조도Sham조17％각조비교차이유통계학의의，P＜0.05。BUO+ CAN조여BUO조상비뇨량현저감소，(55±5)μl·min-1 ·kg-1비(92±7)μl·min-1 ·kg-1，뇨삼투압현저증고(783±47) mosmol/kgH2O비(636±55) mosmol/kgH2O，혈장철고동함량현저강저(2.8±0.5) nmol/L비(4.1±0.2)nmol/L，신장AQP2표체증고，각조비교차이유통계학의의，P＜0.05。결론 ANG Ⅱ수체길항제가통과조지AQP2하조규정수대사문란，보호신공능，제시ANG Ⅱ통과조절신장AQP2표체삼여수뇨관경조후신장수대사변화。
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 ± 3μl min 1 kg-1 ,n = 8;P＜0. 05) and a reduced urine osmolality(BUO vs. Sham: 636 ± 55 vs. 1 853 ± 163 mosmol/kgH2O,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 μl min-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/kgH2O,n = 8; P＜0. 05) and plasma 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 AQP2compared 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. Angiotensin Ⅱ is involved in the pathophusilogical changes in renal function after release of BUO.