糖尿病肾病患者血清晚期蛋白氧化产物水平及其临床意义的研究

The serum level of advanced oxidation protein products(AOPP) and its role in the genesis and development of diabetic nephropathy

目的通过检测不同时期糖尿病肾病(DN)患者血清晚期蛋白氧化产物(AOPP)水平,分析其与超氧化物歧化酶(SOD)及单核细胞趋化蛋白-1(MCP-1)的相关性,研究蛋白氧化与DN的关系及临床意义。方法 66例2型糖尿病(T2DM)患者根据尿白蛋白排泄率(UAER)将患者分为以下3组:正常白蛋白尿(N-UAlb)组20例(UAER<30 mg/24h)、微量白蛋白尿(M-UAlb)组24例(UAER 30～300mg/24h)和大量白蛋白尿(L-UAlb)组22例(UAER>300 mg/24h),并与20名正常对照(NC)组比较。用Wikto-sarsat介绍的方法改进后测定各组的血清AOPP水平,黄嘌呤氧化酶法测定SOD水平,ELISA法测定血清MCP-1水平。结果随着UAER的增加,血清中AOPP水平逐渐增高,各组间比较均有统计学意义(P<0.05);血清中SOD水平逐渐降低,除N-UAlb组与NC组间相比外,其余各组间比较均有统计学意义(P<0.05);血清MCP-1水平逐渐增加,除L-UAlb组与M-UAlb组间相比外,其余各组间比较均有统计学意义(P<0.05)。相关分析表明血清AOPP与SOD呈显著负相关,与BUN、Cr、TG、UAER呈显著正相关,与MCP-1、HDL-C、LDL-C、TC、HbA1c、BMI无相关性。血清SOD与BUN、Cr、UAER、MCP-1呈显著负相关,与TG、TC、LDL-C、HDL-C、HbA1 c、BMI无相关性。多重线性回归分析结果显示Cr、TG、UAER对AOPP有显著影响;Cr、UAER、MCP-1对SOD有显著影响。结论增加的蛋白氧化损伤及氧化应激状态可能在DN的发生发展中起重要作用,增加的蛋白氧化应激可能与DN的氧化应激状态和慢性炎症相关。

Objective To investigate the changes of serum level of AOPP during the different stages of diabetic nephropathy. Methods Sixty-six cases with T2DM were divided into three groups： normal albuminuria group（less than 30mg/24h, 20 cases）, microalbuminuria group（between 30mg/24h and 300mg/24h, 24 cases）, macroalbuminuria group（more than 300mg/24h, 22 cases ）. The concentration of serum AOPP was measured by modified Wikto-Sarsat , while SOD by Xanthine oxidase test , MCP-1 by ELISA assay. Results The level of AOPP increased along with the increase of UAER and there were significant differences in AOPP among the three groups（P〈0. 05）. The level of SOD decreased along with the increase of UAE and there were significant differences between the four groups（P〈0. 05） . The level of MCP-1 increased with the increase of UAE and there were significant differences among the three groups（P〈0. 05） except the groups of M-UAlb and L-UAlb. The AOPP was negatively correlated with SOD and positively correlated with BUN, Cr, TG and UAER , while had no significant correlation with MCP-1, HDL-C, LDL-C, TC, HbAI c and BML The SOD was negatively correlated with BUN, Cr, UAE and MCP-1, while had no significant correlation with TG, TC, LDL-C, HDL-C, HbAle and BMI. In multiple regression, AOPP was significantly correlated with Cr, TG and UAER, and the SOD was significantly correlated with Cr, UAER and MCP-1. Conclusion The enhanced protein oxidation and oxidative stress may play an important role in the initiation and progression of DN. The enhanced protein oxidation may related to oxidative stress and chronic inflammation in DN.