Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure
Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure
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DOI：
10.2119/2005-00034.ueda
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发表时间：
2006-07-01
影响因子：
5.7
通讯作者：
Okuda, Seiya
中科院分区：
文献类型：
--
作者：
Ueda, Seiji;Yamagishi, Sho-ichi;Okuda, Seiya
晚期糖基化终产物（AGEs）是衰老的大蛋白衍生物，在慢性肾功能衰竭（CRF）患者中以加速的速度形成。AGE在血浆和血管组织中的形成和积累加速了这种破坏性疾病的动脉粥样硬化。AST-120是一种口服吸附剂，通过去除尿毒症毒素来减缓CRF的进展。最近，AST-120也被报道可以减少动脉粥样硬化的进展。然而，AST-120是否降低血清AGEs水平并随后发挥动脉粥样硬化保护作用仍有待阐明，本研究纳入了10例非糖尿病性CRF患者。在整个研究过程中，所有患者都保持常规的治疗性饮食和药物治疗。采用酶联免疫吸附法测定AST-120治疗前后血清AGE水平。通过半定量RT-PCR分析患者源性血清对培养的人脐静脉包膜细胞（HUVECs）动脉粥样硬化相关基因表达的影响，结果显示，连续3个月给予AST-120 （6 g/天）可显著降低非糖尿病CRF患者血清AGEs水平，而未给予AST-120治疗的年龄和肾功能匹配的CRF患者血清AGE水平保持不变（n = 6）。与治疗前相比，AST-120治疗后患者血清中AGEs受体、单核细胞趋化蛋白-1和血管粘附分子-1的mRNA水平显著降低。此外，在体外，AST-120被发现吸附羧甲基赖氨酸（CML），这是一种表征良好的消化食物来源的AGEs。这项研究表明，AST-120的动脉粥样硬化保护特性可以归因于，至少部分归因于其通过吸收CML降低年龄的能力。
Advanced glycation end products (AGEs) are senescent macroprotein derivatives that are formed at an accelerated rate in patients with chronic renal failure (CRF). AGE formation and accumulation in plasma and vascular tissues contribute to accelerated atherosclerosis in this devastating disorder. AST-120 is an oral adsorbent that attenuates the progression of CRF by removing uremic toxins. Recently, AST-120 has been reported to reduce the progression of atherosclerosis as well. However, whether AST-120 decreases serum levels of AGEs and subsequently exerts atheroprotective properties remains to be elucidated, Ten nondiabetic CRF patients were enrolled in this study. All patients were kept on regular therapeutic diet and medications throughout the study. Serum AGE levels before and after AST-120 treatments were measured using enzyme-linked immunosorbent assay. Effects of patient-derived serum on atherosclerosis-related gene expression in cultured human umbilical vein enclothelial cells (HUVECs) were analyzed by semiquantitative RT-PCR, Administration of AST-120 (6 g/day) for 3 months significantly decreased serum levels of AGEs in non-diobetic CRF patients, whereas AGE levels remained unchanged in age- and renal function-matched CRF patients without AST-120 treatment (n = 6). Patient serum after AST-120 treatment significantly reduced mRNA levels of receptor for AGEs, monocyte chemoattractant protein-1, and vascular adhesion molecule-1 in HUVECs compared with serum before treatment. Moreover, in vitro, AST-120 was found to adsorb carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs. This study suggests that atheroprotective properties of AST-120 can be ascribed, at least in part, to its AGE-lowering ability via absorption of CML.