氯沙坦降低糖尿病肾病患者蛋白尿的机制  

Effects of Losartan on Albuminuria in Patients with Diabetic Nephropathy and the Mechanism

作　　者：胡春[1] 张霞[1] 金惠敏[1,2] 陈佩华[1] 朱士建[1] 顾慧益[1] 张玉梅[1] 潘瑜[1] 

机构地区：[1]上海交通大学附属第三人民医院肾脏内科,上海201900 [2]复旦大学附属上海浦东医院肾脏内科,上海201300

出　　处：《中国临床医学》2013年第2期157-160,共4页Chinese Journal of Clinical Medicine

基　　金：上海市教委科研项目(编号:10YZ35);上海市宝山区科学技术委员会科研项目(编号:09-E-2)

摘　　要：目的:探讨氯沙坦减轻糖尿病肾病(diabetic nephropathy,DN)患者蛋白尿的机制。方法:60例2型糖尿病肾病合并高血压患者,采用随机数法分为氯沙坦组(n=30)和氨氯地平组(n=30)。氯沙坦组给予氯沙坦100 mg/d,氨氯地平组给予氨氯地平5 mg/d,治疗24个月(2009～2011年)。两组患者治疗前后均测量血压,检测血肌酐(serum creatinine,SCr)、空腹血糖、糖基化血红蛋白(glycated hemoglobulin,HbA1c),采用酶联免疫吸附试验检测血、尿8-羟基脱氧鸟苷(8-hydroxy-2′-deoxy-guanosine,8-OHdG)和硝基酪氨酸(nitrotyrosine,NT)、血超氧化物歧化酶(superoxide dismutase,SOD)活性水平;采用免疫比浊法检测血超敏C反应蛋白(high sensitivity C-reactive protein,hsCRP)和24 h尿微量白蛋白;采用硝酸还原酶法检测一氧化氮(nitric oxide,NO)活性。结果:两组患者在治疗后收缩压、舒张压均明显改善,但两组差异无统计学意义。氯沙坦组治疗后24 h尿微量白蛋白、空腹血糖、血HbA1c、hsCRP、血和尿8-OHdG、NT和NOX较治疗前明显下降,SOD活性水平明显上升,差异均有统计学意义。氨氯地平组治疗前后各指标差异无统计学意义。氯沙坦组较氨氯地平组空腹血糖、血HbA1c、24 h尿微量白蛋白、hsCRP显著下降(P<0.01),血NT、NO、8-OHdG明显下降而SOD明显上升(P<0.01)。Pearson相关分析显示,血清SOD活性水平分别与空腹血糖、HbA1c、hsCRP、TNF-α,NF-κBp65(%)、24 h尿微量白蛋白呈负相关。结论:氯沙坦能显著改善糖尿病肾病患者血糖、尿微量蛋白水平,其作用机制可能与激活SOD有关。Objective：To explore the influence of losartan on albuminuria in patients with diabetic nephropathy（DN）. Methods： A total of 60 patients with type 2 DN and hypertension were assigned randomly into two groups. Losartan group（n = 30） received 100 mg losartan daily, while amlodipine group（n = 30） received 5 mg amlodipine daily. Both groups have been treated for 24 months. The levels of serum creatinine, fasting blood gIucose,glycated hemoglobulin（HbAlc） were measured by routine chemical method. The urine and serum 8-hydroxy-2＇-deoxyguanosine （8-OHdG）, nitrotyrosine （NT） and serum superoxide dismutase（SOD） activity were measured by enzyme linked immunosorbent assay（ELISA）. High sensitivity C-reactive protein （hsCRP） and 24 h urine albumin were measured by immunoturbidimetric assay. The activity of nitric oxide（NO） was assayed by nitrite reductase. Results： Systolic and diastolic pressures in both losartan group and amlodipine group reduced significantly after treatment（P〈0.01）. 24 h urine albumin and the levels of fasting blood glucose, HbAlc, bsCRP, 8-OHdG and NT decreased in losartan group alter treatment,but serum SOD activity was enhanced. There was no significant difference in those indexes before and after treatment in amlodipine group. A significant correlation was observed between the increase in serum SOD activity and the reduction in albuminuria. Conclusions： Losartan has an antioxidative effect in type 2 diabetic nephropathy because of its ability to enhance SOD activity.

关 键 词：氯沙坦 糖尿病肾病 一氧化氮 8-羟基脱氧鸟苷 超氧化物歧化酶活性 

分 类 号：R587.1[医药卫生—内分泌]