【作者】 牛红心；

【导师】 张训； 侯凡凡；

【作者基本信息】 第一军医大学 ， 内科肾脏病学， 2006， 博士

【摘要】 研究背景 心血管疾病(CVD)是慢性肾脏病(CKD)患者最重要的死亡原因，占总死亡率的44％～51％，其病因由动脉粥样硬化(AS)导致的闭塞性血管病变又占半数以上。CKD患者已被认为是心血管事件的“极高度危险人群”。在导致CVD高发率的众多原因中，CKD患者体内普遍存在的高氧化应激水平与AS之间的关系是近年来受到广泛关注的研究领域。晚期氧化蛋白产物(AOPP)是在尿毒症患者血浆中发现的蛋白质氧化交联产物，是氧化应激过程中由激活的中性粒细胞髓过氧化物酶产生的次氯酸(HClO)作用于蛋白质而形成的，在体外用HClO作用于正常人血浆或纯化的人血清白蛋白(HSA)亦可得到与尿毒症病人血浆中类似的AOPP。已发现在轻度慢性肾功能不全(CRI)病人体内AOPP水平即开始升高，且随肾功能恶化进行性升高，与血清肌酐水平呈正相关，维持性透析者达到顶峰。血浆AOPP水平与双酪氨酸、戊糖素、新喋呤等氧化应激标志物呈正相关，与谷胱甘肽过氧化物酶等抗氧化剂呈负相关，因此AOPP被认为是反映慢性肾衰竭(CRF)时氧化应激的标志物。不仅如此，在体外AOPP可以刺激单核细胞和多形核白细胞呼吸爆发和细胞因子合成，且反应强度与HSA被HClO氧化修饰的程度成正比，提示AOPP本身也是一种新型的炎症介质，能诱导或加重氧化应激。更多还原

【Abstract】 BackgroundAdvanced oxidation protein products (AOPPs) were the final cross-linking products of protein oxidation which had been found in the plasma of dialysis patients in 1996. In vitro, exposure of purified plasma albumin to chlorinated oxidants triggered the formation of AOPPs in an oxidant concentration-dependent manner. Serum AOPPs levels elevated in patients with mild chronic renal insufficiency (CRI) and increased with the depravation of renal function, culminating in patients on maintaining dialysis. Serum AOPPs levels were closely related to dityrosine, a marker of protein oxidation, and neopterin, one of the monocyte activation markers. A negative correlation was also found between serum AOPPs levels and glutathione peroxidase (GSH-Px). Therefore, AOPPs were thought to be a novel marker of oxidative stress in chronic kidney disease (CKD) patients. Moreover, AOPPs triggered the oxidative burst and the synthesis of inflammatory cytokines in neutrophils as well as in monocytes in vitro and the intensity of the respiratory burst was dependent on the level of protein oxidation, indicating that AOPPs might act as a更多还原