Inhibition of intra-peritoneal carbonyl stress by carbonyl adsorbing beads or carbonyl stress inhibitor

羰基吸附珠或羰基应激抑制剂对腹腔内羰基应激的抑制

基本信息

批准号：
17590847
负责人：
KAKUTA Takatoshi
金额：
$ 2.37万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

The molecular mechanisms underlying the peritoneal membrane (PM) failure remain elusive. Chronic uremia by itself modifies the PM and increases the effective peritoneal surface area (EPSA). PM deterioration during peritoneal Dialysis (PD) results, at least in part, from the accumulation of reactive carbonyl compounds (RCOs) present in heat-sterilized PD fluid. We have proposed two hypothetical approaches to reduce intra-peritoneal carbonyl stress. The more recently identified pyridoxamine, ARB and its analog a new class of advanced glycation end products (AGEs) inhibitors, traps RCO precursors by its amino group. Another approach to reduce intra-peritoneal carbonyl stress is the RCO adsorbing beads. Pyridoxamine, given in uremic rats with PD, significantly improved functional and structural alterations. This improvement was accompanied by reduction of AGE accumulation and of angiogenic cytokines expressions. Mixed with glucose PD fluid, pyrazolinones-polyethyleneimine, with cellulose beads (PPCB) markedly lowers RCOs (??dicarbonyls and aldehydes) and inhibits the generation of pentosidine, an AGE, to levels similar to those of filter-sterilized PD fluid. Its effectiveness is more than one order of magnitude above those of previously developed beads.

腹膜膜（PM）衰竭背后的分子机制仍然难以捉摸。慢性尿毒症本身会修饰PM并增加有效的腹膜表面积（EPSA）。腹膜透析（PD）期间的PM恶化至少部分是由于热毒性PD液中存在的反应性羰基化合物（RCO）的积累。我们提出了两种假设方法来减少腹膜内羰基应激。最近发现的吡id胺ARB及其类似物是由其氨基组组成的一类新的晚期糖基化末端产品（年龄）抑制剂，诱捕RCO前体。减少腹膜内羰基应激的另一种方法是RCO吸附珠。吡id胺，在具有PD的尿毒症大鼠中给出，可显着改善功能和结构改变。这种改善伴随着年龄的积累和血管生成细胞因子表达的减少。与葡萄糖PD液，吡唑啉酮 - 多甲基亚胺混合，纤维素珠（PPCB）显着降低了RCO（?? dicarbonyls and醛和醛），并抑制戊烷的产生，一种年龄，与过滤的PD液体相似。它的有效性比先前开发的珠子的效率超过一个数量级。