慢性肾脏病血清晚期糖基化终产物与氧化应激的关系

目的 探讨慢性肾脏病（Chronic Kidney Disease,CKD）患者血清晚期糖基化终产物（Advanced Glycosylation End Products,AGEs）与氧化应激的关系.方法 CKD组以78例住院患者为研究对象（除外糖尿病肾病或合并糖尿病的患者）,将CKD组按评估的肾小球滤过率（evaluated glomerular filtration rate,GFR）分为终末期肾脏病组（GFR＜ 10 ml/min/1.73 m2）和非终末期肾脏病组（GFR≥10 ml/min/1.73 m2）两组.以38例健康体检的正常人为对照组,血清AGEs采用竞争性ELISA法测定;血清晚期蛋白氧化产物（advanced oxidation protein products,AOPPs）测定采用分光光度法测定;血浆总抗坏血酸（Total Ascorbic Acid,TAA）和氧化型抗坏血酸（Dehydroascorbic Acid,DHAA）采用高效液相色谱法（High Performance Liquid Chromatography,HPLC）结合电化学检测器测定;eGFR应用预测方程（MDRD简化公式）.应用SPSS11.0软件包进行统计分析.结果 CKD患者和健康人相比存在血清AGEs潴留（t=11.621,P＜ 0.001）;终末期肾脏病患者、非终末期肾脏病患者及健康人群血清AGEs水平相比有显著性差异（组间比较,F=42.871,P＜0.001）,eGFR与血清AGEs存在负相关（r=-0.304,P＜0.05）.CKD患者血清AOPPs水平比健康人明显增高（t=5.310,P＜0.001）.CKD患者和健康人相比血浆DHAA水平存在显著性差异（t=4.295,P＜0.001）,血浆氧化型抗坏血酸与总抗坏血酸浓度的比值（DHAA/TAA）差异有统计学意义（t=4.924,P＜0.001）.结论 CKD患者存在血清AGEs潴留,CKD患者GFR的下降导致AGEs清除减少及其存在的氧化应激与羰基应激状态导致AGEs生成增加是AGEs潴留的重要原因;对氧化应激状态的干预是减少AGEs潴留及其病理损害的重要环节.

Relationship Between Advanced Glycosylation end Products and Oxidative Stress in Chronic Kidney Disease

Objective To investigate the realationship between advanced glycosylation end products（AGEs）and oxidative stress in chronic kidney disease（CKD）.Methods 78 patients with CKD and 38 healthy volunteers were involved in the study.The serumAGEswere measured by using competitive enzyme- linked immunosorbent assay（ELISA）. The serum advanced oxidation protein products（AOPPs）were determined by using Spectrophotometry. The level of plasma Total ascorbic acid（TAA）and dehydroascorbic acid（DHAA）were determined by high performance liquid chromatography（HPLC）with electrochemical detection.GFR was estimated using the simplified prediction equation derived from the Modification of Diet in Renal Disease（MDRD） Study.Results The serum AGEs in patients with CKD were significantly higher than those in normal subjects（t= 11.621,P〈0.001）. The serum AGEs in end stage renal disease（ESRD）group（GFR 10 ml/min/1.73 m2）and in non- ESRD group（GFR≥ 10 ml/min/1.73 m2）both were significantly higher than those in normal subjects（P〈0.001）.There was significant negative correlation between the level of serum AGEs and eGFR（r =- 0.304,P〈0.05）.The serum AOPPs in patients with CKD were significantly higher than those in normal subjects（t= 5.310,P〈0.001）.In patients with CKD in comparison with normal subjects,there was significant difference in the level of plasma TAA（t= 2.307,P〈0.05）,DHAA（t= 4.295,P〈0.001）, DHAA/TAA（t= 4.924,P〈0.001）.Conclusion AGEs also accumulate in CKD patients. Augmented oxidative stress and reactive carbonyl compounds derived from carbohydrates might accelerate AGEs formation in CKD patients. Management to inhibit oxidative stress must be a effective means to diminish AGEs formation in CKD patients.