血管紧张素Ⅱ受体阻断剂对慢性肾脏病患者肾素-血管紧张素系统表达的影响

摘要

目的:研究血管紧张素Ⅱ受体阻断剂( angiotensin Ⅱ receptor blocker,ARB)对慢性肾脏病(chronic kidney disease,CKD)患者循环和肾脏肾素-血管紧张素系统(renin-angiotensin system,RAS)表达的影响.方法:行肾脏活组织检查且2个月内未曾服用血管紧张素转换酶抑制剂的CKD患者,其中2周内ARB治疗的患者17例(ARB治疗组),另选取2周内未应用ARB治疗的患者17例(空白对照组),根据年龄、性别、血压、估算肾小球滤过率(eGFR)、24 h尿蛋白、尿钠等进行配对.采用放射免疫法和酶联免疫吸附分析(ELISA)方法测定血、尿RAS组分的浓度,并采用免疫组织化学方法评价肾脏肾素、血管紧张素原( AGT)、血管紧张素Ⅱ(AngⅡ)和血管紧张素Ⅱ受体的表达.分析ARB对血、尿和肾组织RAS表达的影响.结果；ARB治疗组与空白对照组在性别、年龄、eGFR、24 h尿蛋白、尿钠和血压等方面均显著差异.ARB治疗组血浆AngⅡ高于空白对照组[(63.09±15.14) pg/mL比(53.66±8.33) pg/mL,P＜0.05],肾内肾素免疫组织化学染色面积高于空白对照组[(48.65±19.58)％比(30.29±24.98)％,P＜0.05].ARB治疗组肾内AGT、AngⅡ和血管紧张素Ⅱ1型受体免疫组织化学染色面积略低于空白对照组,但差异无统计学意义.结论:ARB治疗对循环和肾脏局部RAS表达的影响不同,可使循环AngⅡ升高,并可能抑制肾脏局部AngⅡ的表达.%Objective:To analyze the effect of angiotensin Ⅱ receptor blocker(ARB) on renin-angiotensin systemCRAS) in chronic kidney disease(CKD) patients. Methods: Among CKD patients who performed renal biopsy in Shanghai Zhongshan Hospital and had not received angiotensin converting enzyme inhibitor during last 2 months, 17 patients had received ARB during last two weeks (ARB group). They were matched pair with other patients who had not received ARB during last two weeks according to age, sex, blood pressure, estimated glomerular filtration rate (eGFR) , urinary protein of 24 hours and urinary sodium (control group). We measured plasma renin activity, plasma and urinary angiotensinogenC AGT), angiotensin Ⅱ (AngⅡ ) and aldosterone by RIA or ELISA and assessed expression of intrarenal renin, AGT, Ang Ⅱ and angiotensinⅡ receptor by immunohistochemistry staining(IHCS) in order to determine the difference of general and intrarenal RAS activity between two groups. Results: There was no difference on sex, age, blood pressure, eGFR, urinary protein of 24 hours and urinary sodium between two groups. Average plasma Ang Ⅱin ARB group was higher than that in control group (63. 09 ± 15. 14 pg/mL vs. 53. 66 ±8. 33 pg/mL, P<0. 05). Positive IHCS area of intrarenal renin in ARB group was higher than that in control group (48. 65% ± 19. 58% vs. 30. 29% ± 24. 98% ,P<0. 05). Positive IHCS area of intrarenal AGT, Ang Ⅱ and angiotensinⅡ type 1 receptor in ARB group was lower than those in control group, but the difference had no statistical meaning. Conclusions: ARB has different influence on the activity of general and intrarenal RAS. ARB can elevate general angiotensin II activity and probably can inhibit the expression of intrarenal angiotensin Ⅱ .