西罗莫司对双侧输尿管梗阻大鼠水电解质代谢紊乱的保护作用  

Protective effect of sirolimus on water-electrolyte imbalance following bilateral ureteral obstruction in rats

作　　者：张岩[1] 杨梅[1] 徐自强[1] 杨宇[1] 郑少玲[1] 杨亦荣[1] 

机构地区：[1]温州医学院附属第一医院器官移植中心,325000

出　　处：《中华泌尿外科杂志》2011年第10期666-670,共5页Chinese Journal of Urology

基　　金：浙江省自然科学基金（Y2110944）

摘　　要：目的探讨两罗莫司对双侧输尿管梗阻（BUO）大鼠水电解质代谢紊乱及肾脏卜皮钠通路γ（γ-ENaC）、Na^＋ -K^＋-ATP酶及水通道蛋白2（AQP2）蛋白的影响。方法Wistar大鼠48只，随机分为假手术组、B150组和四罗莫司组，每组16只。11150组和西罗莫司组大鼠结扎双侧输尿管制作BUO模型，似下术纰仅游离双侧输尿管后缝合。BUO组及西罗莫司组双侧输尿管梗阻24h后解除梗阻。西罗莫司组每大西罗莫司口服液（2．5ml／次）灌胃，假于术组及UUO组用同体积生理枯水灌坩。于术后4、7d测量3组大鼠尿量并留取尿液进行生化分析；术后4、7d抽取动脉血化验，同时取出双侧肾脏，采用免疫组化及蛋白质印迹法检测肾脏γ-ENaC、Na^＋ -K^＋-ATP酶及AQP2蛋白的表达．结果BUO组大鼠输尿管梗阻解除后4、7d尿量分别为（85．31±13．15）、（66．39±10．56）ml，艟普多于假手术组（35．36±7．74）、（33．90±8．03）ml及西罗莫司组（69．81±10．70）、（48．57±9．01）ml；球钠浓度（42．17±7．35）、（43．63±18．39）mmol／L，显著低于假于术组（170．56±18．39）、（172．52±7．35）mmol／L．及西罗莫司组（76．18±13．20）、（134．28±13．20）mmol／L，3组间比较差异均仃统计学意义（P〈0．05）。两罗莫司绢4、7d肾脏γ-ENaC表达麓分别为2．09±0．32、2．27±0．35，Na^＋ -K^＋ -ATP分别为2．41±0．48、2．67±0．43，AQP2分别为2．17±0．45、2．63±0．28，显著高于同时间点的BUO组（1．28±0．21、1．45±0．17，1．99±0．28、2．18±0．24，0．93±0．22、1．31±0．16），低于同时间点假手术组（2．58±0．51、2．60±0．56，2．89±0．53、2．97±0．66，3．05±0．63、3．10±0．67），3组间比较差异均有统计学意义（P〈0．05）。结论γ-ENaC、Na^＋ -K^＋-ATP酶及AQP2蛋白水平降低町能是泌尿系梗阻后肾小管性钠嘲吸收障碍、低渗性�Objective To explore the molecular mechanism of renal function defects after urinary obstruction and investigate the effect of sirolimus on the expression of γ-ENaC, Na ＋ K ＋ ATPase and AQP2, and its mechanism of renal Water-Electrolyte imbalance ft）llowing bilateral ureteral obstruction （BUO） in＂ rat kidneys. Methods Forty-eight rats were randomly divided into a sham operation group （sham group） , a BUO group, and a sirotimus treatment after BUO group. Bilateral ureters were exposed and occluded with ligature in the BUO and sirolimus treatment groups. Twenty-four hours later, the obstructed ureters were decompressed by removal of the ligature. The sham animal group underwent identical surgical procedures, but the ureter was simply dissected without removal of the ligature. The sirolimus treatment groups was given sirolimus intragastriely 0.4 ml per day （2 mg/kg·d） from the day before surgery until the rats were scarifled. The sham and BUO groups were given the same volume of intragastric saline. The urine and blood were collected at 4 d, 7 d after surgery, and the functional data were observed. The expression of γ-ENaC, Na^＋- K^＋- ATPase and AQP2 were examined by immnohistochemistry and immunoblotting. Results On day four and seven post ureteral obstruction release, urine volume in the BUO group were （85.31 ± 13.15, 66.39 ±10.56 ml）, significantly higher than that of sham operation （35.36 ±7.74, 33.90 ± 8.03 ml） and sirolimus treatment groups （69.81 ± 10.70 ml, 48.57± 9.01 ml） （P 〈 0. 05 ）. Urine sodium concentrations in the BUO group were （42. 17 ± 7.35 mmol/L, 43.63 ±18.39 mmol/L） , significantly lower than that of sham operation （ 170. 56 ±18. 39 mmol/L, 172. 52± 7. 35 mmol/L） and sirolimus treatment groups （76.18±13.20 mmol/L, 134.28 ± 13.20 mmol/L） , P 〈 0.05. Immunoblotting assay showed that, on day four and seven post rats ureteral obstructions were released, integral optical density of 3,-ENaC （2.09 ± 0.32, 2.27±0.35） , Na＋K�

关 键 词：西罗莫司 水电解质失调 动物实验 

分 类 号：R693[医药卫生—泌尿科学]