尾加压素II在Dahl盐抵抗大鼠血压调节中的作用及机制研究  

Roles of urotensin II in the regulation of blood pressure in Dah Dah1 salt resistant rat

作　　者：吴菲[1] 张爱华[1] 

机构地区：[1]北京大学第三医院肾内科,北京100191

出　　处：《中国血液净化》2016年第4期235-240,共6页Chinese Journal of Blood Purification

基　　金：国家自然基金委项目资助(项目编号81170706;81341022;81570663)

摘　　要：目的我们既往在容量超负荷而血压维持正常的腹膜透析患者中,发现血浆尾加压素Ⅱ（urotensinⅡ,UⅡ）水平升高,提示UⅡ在这类患者的血压调节中发挥作用,但其调节机制未明。本研究选取与容量超负荷而血压维持正常的特性相类似的Dahl盐抵抗大鼠模型,研究其在高盐负荷下血压调节,循环及肾脏的UII表达,探讨UⅡ在Dahl盐抵抗（dahl salt-resistant,SR）大鼠血压调节中的作用及机制。方法 Dahl盐敏感（dahl salt-sensitive,SS）和SR大鼠,UII受体敲除的小鼠及C57BL/6野生型小鼠,高盐负荷6～8周,检测基线及高盐负荷6～8周后血压,血浆UII,尿UII,肾脏及主动脉的UII及UII受体的m RNA及蛋白的表达,24h尿钠排泄,24h肌酐清除率。结果 1高盐负荷6周后SS大鼠血压显著高于SR大鼠[（160±13）mm Hg比（114±6）mm Hg,t=8.191,P〈0.001];SR大鼠血浆UII水平显著高于SS大鼠[（60.3±3.8）pg/ml比（51.6±13.5）pg/ml,t=2.450,P=0.021]。高盐负荷4周后SR大鼠尿UII的浓度显著高于SS大鼠[（236.90±27.89）ng/g比（114.70±6.28）ng/g,t=3.898,P=0.003）],24h尿钠排泄量[4周时：（3.243±0.306）mmol比（1.753±0.127）mmol,t=3.942,P=0.010];6周时：（2.870±0.134）mmol比（1.713±0.077）mmol,t=3.942,P〈0.001]和6w时肌酐清除率亦显著升高[（6.532±0.269）ml/min比（2.632±0.172）ml/min,t=12.210,P〈0.001]。2高盐负荷6w后,SR大鼠的肾脏UII受体（现称为UT）的蛋白表达明显高于SS大鼠[（0.059±0.008）比（0.036±0.001）,t=4.540,P=0.010],UII及受体的表达主要位于肾小管上皮细胞3在高盐饮食后第4周,UII受体敲除的小鼠收缩压显著高于野生普通型小鼠[（113±3）mm Hg比（102±4）mm Hg,=4.750,t P=0.003],而第4周24h尿钠排泄量[（3.11±0.60）μmol比（4.29±0.68）μmol,t=-2.785,P=0.036]及第2周肌酐清除率显著降低[（0.23±0.02）ml/min比（0.11±0.01）ml/min,t=3.018,P=0.016]。结论本研究首次证实UII在高盐负荷后盐抵抗大鼠Objective Our previous study suggests that urotensin II（UII） plays a role in vasodilation when fluid volume in the body increases. To elucidate the role of UII in blood pressure regulation, we conducted this study using animal models that resemble the hemodynamic profiles of volume resistant and volume sensitive patients. In addition, a UII receptor knockout mouse model was established. Methods Dahl salt resistant（SR） rats, Dah1 salt sensitivity（SS） rats, wild type（WT） mice, and UII receptor knock out（KO） mice were used in this study. After placing these four groups of animals on a high salt diet for 6 or 8 weeks, renal tissue was used to perform immunochemistry staining, real time PCR, and western blot to measure UII level in kidney. Results After high salt diet for 6 weeks, systolic blood pressure was significantly higher in SS group than in SR group（160±13 mm Hg vs. 114±6 mm Hg, t=8.191, P〈0.001）. Compared with SS rats, SR rats had higher plasma UII（60.3±3.8 vs. 51.6±13.5 pg/ml, t=2.450, P=0.021）, urinary UII（236.9±27.89 ng/g vs. 114.70 ± 6.28 ng/g, t=3.898, P=0.003）, 24 hours urinary sodium excretion（4w： 3.243 ± 0.306 mmol vs.1.753 ± 0.127 mmol, t=3.942, P=0.010; 6w： 2.870 ± 0.134 mmol vs. 1.713 ± 0.077 mmol, t=3.942, P〈0.001）,and urinary creatinine clearance（6w： 6.532±0.269 ml/min vs. 2.632±0.172 ml/min, t=12.210, P〈0.001）. After high salt diet for 6 weeks, more UII receptor was expressed in renal tubular epithelia of SR rats as compared with those of SS rats（0.059±0.008 vs. 0.036±0.001, t=4.540, P=0.010）. After high salt diet for 8 weeks,systolic blood pressure was significantly higher in KO mice than in WT mice（113 ± 3 mm Hg vs. 102 ± 4mm Hg, t=4.750, P=0.003）. Conclusions The present results first demonstrate that UII can play a role in the regulation of blood pressure in Dah1 SR rats, probably through the effects of UII on ateriole dilatation and promotion of sodium excretion from renal tubules.

关 键 词：尾加压素Ⅱ高血压 盐敏感 盐抵抗 尾加压素Ⅱ 受体基因敲除 

分 类 号：R692.5[医药卫生—泌尿科学]