Weiss M F, Scivittaro V, Anderson J M
Department of Medicine, Division of Nephrology, University Hospitals of Cleveland, OH 44106, USA.
Am J Kidney Dis. 2001 May;37(5):970-80. doi: 10.1016/s0272-6386(05)80013-7.
The pathological role of oxidative stress in patients treated by hemodialysis has gained increasing recognition in recent years. Because complications related to vascular access are a major source of morbidity, immunohistochemical evidence of oxidative stress and activation of growth factors were examined in native arteriovenous (AV) fistulae (n = 11) and expanded polytetrafluoroethylene (ePTFE) grafts (n = 15) recovered from hemodialysis patients at the time of surgical revision or resection. To show the presence of oxidative stress in tissues, three markers were chosen: N(epsilon)(carboxymethyl)lysine, a structurally identified advanced glycation end product; 4-hydroxy-2,3-nonenol, a lipid peroxidation product; and redox-active transition metals bound to proteins, a source of Fenton chemistry-generated free radicals. Markers of cell growth and proliferation were endothelin-1 (ET-1), a potent mitogenic peptide implicated in the formation of intimal hyperplasia; transforming growth factor-beta (TGF-beta), a stimulus to vascular cell growth and matrix production; and platelet-derived growth factor (PDGF), a mediator of intimal hyperplasia. All specimens studied showed significant intimal hyperplasia. In general, the neointima close to the vascular lumen of the AV fistula and the pseudointima close to the lumen of the ePTFE graft were positive for oxidative stress markers. At sites of injury, especially in the presence of histological evidence of inflammation and healing, expression of oxidative markers was particularly intense. Prominent staining of PDGF was shown at sites of anastomotic hyperplasia and in neovasculature. TGF-beta was associated with proliferation or repair in both AV fistulae and ePTFE grafts. ET-1 staining was most intense in the neointima and pseudointima. This study showed histochemical colocalization of markers of oxidative stress with growth factors known to contribute to intimal hyperplasia.
近年来，氧化应激在接受血液透析治疗的患者中的病理作用得到了越来越多的认可。由于与血管通路相关的并发症是发病的主要来源，因此对从血液透析患者手术修复或切除时回收的自体动静脉（AV）内瘘（n = 11）和膨体聚四氟乙烯（ePTFE）移植物（n = 15）进行了氧化应激和生长因子激活的免疫组织化学证据检查。为了显示组织中氧化应激的存在，选择了三种标志物：N（ε）（羧甲基）赖氨酸，一种结构确定的晚期糖基化终产物；4-羟基-2,3-壬烯醛，一种脂质过氧化产物；以及与蛋白质结合的具有氧化还原活性的过渡金属，这是芬顿化学反应产生自由基的来源。细胞生长和增殖的标志物是内皮素-1（ET-1），一种与内膜增生形成有关的强效促有丝分裂肽；转化生长因子-β（TGF-β），一种刺激血管细胞生长和基质产生的因子；以及血小板衍生生长因子（PDGF），一种内膜增生的介质。所有研究的标本均显示出明显的内膜增生。一般来说，靠近AV内瘘血管腔的新生内膜和靠近ePTFE移植物管腔的假内膜对氧化应激标志物呈阳性。在损伤部位，特别是在存在炎症和愈合组织学证据的情况下，氧化标志物的表达尤为强烈。PDGF在吻合口增生部位和新生血管中显示出明显的染色。TGF-β与AV内瘘和ePTFE移植物的增殖或修复有关。ET-1染色在新生内膜和假内膜中最为强烈。这项研究表明氧化应激标志物与已知促成内膜增生的生长因子在组织化学上共定位。
