腹膜透析患者肾素血管紧张素Ⅱ水平变化及其在腹膜纤维化中的意义  

Renin and angiotensin Ⅱ levels in peritoneal dialysis patients and its role in peritoneal fibrosis

作　　者：谢静远[1] 王伟铭[1] 任红[1] 陈楠[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,200025

出　　处：《中华肾脏病杂志》2008年第2期91-97,共7页Chinese Journal of Nephrology

基　　金：上海市重点学科建设基金（T0201）;上海市卫生局重点学科建设基金（05111001）;上海市卫生局重点课题（2003ZD002）

摘　　要：目的探讨持续性非卧床腹膜透析（CAPD）患者血浆及腹腔局部肾素血管紧张素系统（RAS）的变化及其在腹膜纤维化中的意义。方法选取腹透感染组和非感染组CAPD患者25例，非感染患者根据透析龄分为≥6月组和〈6月组。应用放射免疫法检测CAPD患者腹透透出液和血浆中肾素及血管紧张素Ⅱ（AngⅡ）的浓度。以不同浓度D，葡萄糖（0．3％、1．5％、2．5％）、甘露醇（1．5％、2．5％）及AngⅡ（0、1、10、100、1000nmol／L）刺激大鼠腹膜间皮细胞（RPMC），放射免疫法检测细胞上清液AngⅡ浓度变化；实时定量PCR方法观察AngⅡ1型受体（AT1）、血管紧张素转化酶（ACE）、转化生长因子β1（TGF-β1）、结缔组织生长因子（CTGF）mRNA的表达；Western印迹法检测TGF—β1及CTGF蛋白的表达；EHSA法检测上清液中TGF—β1的变化。结果CAPD患者腹透透出液中未检测到肾素。感染及≥6月组的CAPD患者透出液中AngⅡ的浓度分别为（151．99±114）pmol／L和（14．17±41．5）pmol／L，分别为非感染[（7．98±12．69）pmol／L]及〈6月组[（2．18±5．62）pmol／L]的19倍及6．5倍（P〈0．01或P〈0．05）。高糖腹透液（2．5％）注入4h后，CAPD患者循环中肾素及AngⅡ浓度分别为[（4．30±8．48）和（54．19±34．43）pmol／L]，是基础水平的4．06倍和1．21倍（P〈0．01）。高糖组（2．5％）RPMC AT1、ACE mRNA和上清液AngⅡ浓度分别为低糖组（0．3％）的2．61、2．62和2．01倍（P〈0．05）。AngⅡ可在mRNA和蛋白水平上调RPMC表达TGF-β1与CTGF，呈剂量依赖性，100nmol／L组TGF-β1mRNA及蛋白水平分别为对照组的2．8和2．19倍（P〈0．05）；1000nmol／L组CTGFmRNA及蛋白水平分别为对照组的4．48倍和2．82倍（P〈0．05）。AngⅡ促进RPMC分泌TGF—β1，呈时间依赖性，刺激24h组TGF—β1的表达量为基础值的3．65倍（P〈0．05）。结论CAPD尤其是腹透�Objective To explore the change of angiotensin Ⅱ （Ang Ⅱ） and renin and its role in peritoneal fibrosis of continuous ambulatory peritoneal dialysis （CAPD） patients. Methods The levels of Ang Ⅱand renin in effluent and serum of CAPD patients were investigated by radioimmunoassay. A reproducible model for culture of rat peritoneal mesothelial cell was established by isolating from rat omenta by enzymatic disaggregation. Levels of mRNA expression of angiotensin Ⅱ type 1 receptor （AT1） and angiotensin-converting enzyme （ACE） in rat peritoneal mesothelial cells （RPMC） were detected with real-time PCR when stimulated by different concentration of D-glucose or mannitol. Concentration of Ang Ⅱ in supernatant of RPMC was tested at the same time by radioimmunoassay. Levels of mRNA and protein expression of transtorming growth factor β1 （TGF-β1） and connective tissue growth factor （CTGF） in RPMC after the stimulation by different concentrations of Ang Ⅱ were examined with real-time PCR and Western blot respectively, then TGF-β1 in supernatant was detected by ELISA. Results No renin was detected in effluent of CAPD patients. Ang Ⅱ levels in the effluent of patients with peritonitis and long time dialysis patients（≥ 6 months） were （151.99± 114.00） pmol/L and （14.17±41.50） pmol/L, which were 19 times and 6.5 times of normal CAPD [（7.98±12.69） pmol/L] and short time dialysis （〈6 months） [（2.18±5.62） pmol/L）] patients respectively （P〈0.01, P〈0.05）. Serum renin and Ang Ⅱ concentration were （4.30±8.48） and （54.19±34.43） pmol/L,which were 4.06 times and 1.21 times of basal level respectively after 4 hours exposure to high glucose dialysis fluid （2.5%）, while the base levels of renin and Ang Ⅱ concentration were （1.06±6.0） pmol/L and （44.72± 19.19） pmol/L respectively （P〈0.01）. High D-glucose （2.5%） enhanced the expression of AT1, ACE mRNA in RPMC and Ang Ⅱ protein in supernatant of RPMC, which were 2.61, 2.

关 键 词：血管紧张素Ⅱ 肾素 转化生长因子Β 结缔组织生长因子 腹膜纤维化 

分 类 号：R692.5[医药卫生—泌尿科学]