Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats
Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats
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DOI：
10.1111/j.1523-1755.2005.00531.x
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发表时间：
2005-09-01
影响因子：
19.6
通讯作者：
Miyata, T
中科院分区：
文献类型：
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作者：
Kakuta, T;Tanaka, R;Miyata, T
背景我们以前认为，与长期腹膜透析相关的腹膜生化改变可能至少部分是由尿毒症循环和葡萄糖腹膜透析液热灭菌引起的活性羰基化合物过载引起的。在本研究中，我们利用尿毒症大鼠模型进行腹膜透析，并评估吡哆胺，最近开发的晚期糖基化终产物（AGE）抑制剂，对腹膜结构，功能和生化改变的保护作用。通过肾次全切除术产生尿毒症大鼠，其中一些进行腹膜透析和/或腹膜内给予吡哆胺。功能性[透析液/血浆比（D/P）（尿素，肌酸酐），D/D-0葡萄糖]，结构（腹膜组织中的血管密度）和分子生物化学[通过高效液相色谱（HPLC）测定戊糖苷（AGE）的形成以及血管内皮生长因子（VEGF）和成纤维细胞生长因子2（FGF-2）的表达，通过半定量聚合酶链反应（PCR）和/或免疫组织化学]评估腹膜的改变。尿毒症腹膜的特点是增加功能面积的交换小溶质之间的血液和透析液，血管增生，增加AGE的产生，和上调表达的血管生成细胞因子。与腹膜透析相关的腹膜改变相似，但比未进行腹膜透析的尿毒症患者更严重。吡哆胺给予尿毒症大鼠腹膜透析显着改善功能和结构的改变。这种改善伴随着AGE积累和血管生成细胞因子表达的减少。尿毒症和腹膜透析过程中产生的腹膜羰基应激可能通过诱导生物活性分子而促进血管增殖，并增加功能面积，最终导致超滤失败。吡哆胺可能对腹膜透析时尿毒症腹膜有保护作用。
Background. We previously suggested that biochemical alterations of peritoneal membrane associated with long-term peritoneal dialysis might be, at least in part, accounted for by reactive carbonyl compounds overload originating both from uremic circulation and heat sterilization of glucose peritoneal dialysis fluid. In the present study, we utilized a uremic rat model on peritoneal dialysis and evaluated the protective effects of pyridoxamine, a recently developed inhibitor of advanced glycation end product (AGE), on structural, functional, and biochemical alterations of peritoneal membrane.Methods. Uremic rats were generated by subtotal nephrectomy, some of which were undergone peritoneal dialysis with dialysate and/or given intraperitoneal pyridoxamine. Functional [dialysate/plasma ratio (D/P)(urea, creatinine), D/D-0 glucose], structural (density of blood vessels in peritoneal membrane tissues), and molecular biochemical [formation of pentosidine, an AGE, by high-performance liquid chromatography (HPLC) assay and expressions of vascular endothelial growth factor (VEGF), and fibroblast growth factor 2 (FGF-2), by semiquantitative polymerase chain reaction (PCR) and/or immunohistochemistry] alterations of peritoneal membrane were assessed.Results. Uremic peritoneal membrane was characterized by an increased functional area of exchange for small solutes between blood and dialysate, vascular proliferation, increased AGE genesis, and up-regulated expressions of angiogenic cytokines. The peritoneal membrane alterations associated with peritoneal dialysis are similar but more severe than those in uremia without peritoneal dialysis. Pyridoxamine given in uremic rats with peritoneal dialysis significantly improved functional and structural alterations. This improvement was accompanied by reduction of AGE accumulation and of angiogenic cytokines expressions.Conclusion. Peritoneal carbonyl stress derived from uremia as well as peritoneal dialysis procedure might contribute to the vascular proliferation through induction of bioactive molecules and to an increased functional area, eventually leading to ultrafiltration failure. Pyridoxamine may be beneficial in protection of uremic peritoneal membrane on peritoneal dialysis.