Department of Nephrology, University of Heidelberg, Germany.
Perit Dial Int. 2010 Jan-Feb;30(1):35-40. doi: 10.3747/pdi.2009.00031.
It has been shown that glucose degradation products (GDP) generated during heat sterilization of peritoneal dialysis (PD) fluids impair the peritoneal membrane locally, then enter the systemic circulation and cause damage to the remnant kidney. Here we examined in subtotally nephrectomized (SNX) rats whether GDP also affect the cardiovascular system.
Standard 5/6 nephrectomy was carried out in Sprague-Dawley rats; other rats were sham operated and left untreated for 3 weeks. Through an osmotic mini-pump, SNX+GDP group received GDP intravenously for 4 weeks; the SNX and the sham-operated groups remained without GDP. The experiment was terminated for all groups 7 weeks postoperatively. We analyzed cardiovascular damage by serum analyses and immunohistochemical investigation.
In SNX+GDP animals, expression of the advanced glycation end product (AGE) marker carboxymethyllysine and receptor of AGE (RAGE) were significantly higher in the myocardium and the aorta compared to the SNX rats. We also found significantly higher levels of apoptosis measured by caspase 3 staining in the cardiovascular system in the SNX+GDP group. Moreover, we observed a more pronounced expression of oxidative stress in the SNX+GDP rats compared to the SNX rats. In serum analyses, advanced oxidation protein products and reactive oxygen species were increased, as was immunohistochemical endothelial nitric oxide synthase.
In addition to local toxic effects, GDP cause systemic toxicity. Here we showed that, in SNX rats, administration of GDP increased cardiovascular damage. In particular, we found increased levels of AGE, RAGE, oxidative stress, and apoptosis. Whether these findings are of clinical relevance has to be further investigated.
已有研究表明，腹膜透析液在高温灭菌过程中产生的葡萄糖降解产物（GDP）会局部损伤腹膜，随后进入体循环，对残余肾脏造成损伤。在此，我们在部分肾切除（SNX）大鼠中观察 GDP 是否也会影响心血管系统。
Sprague-Dawley 大鼠行标准的 5/6 肾切除术；其他大鼠假手术，未经处理 3 周。通过渗透微型泵，SNX+GDP 组大鼠静脉内给予 GDP 4 周；SNX 组和假手术组大鼠不给予 GDP。所有大鼠术后 7 周时终止实验。我们通过血清分析和免疫组织化学研究来分析心血管损伤。
在 SNX+GDP 大鼠中，与 SNX 大鼠相比，心肌和主动脉中晚期糖基化终产物（AGE）标志物羧甲基赖氨酸和 AGE 受体（RAGE）的表达显著升高。我们还发现 SNX+GDP 组大鼠心血管系统中的细胞凋亡标志物 caspase 3 染色水平明显升高。此外，与 SNX 大鼠相比，SNX+GDP 大鼠的氧化应激表达更为明显。在血清分析中，氧化应激产物和活性氧增加，免疫组织化学内皮型一氧化氮合酶增加。
除了局部毒性作用外，GDP 还会引起全身毒性。在此，我们发现，在 SNX 大鼠中，给予 GDP 会增加心血管损伤。特别是，我们发现 AGE、RAGE、氧化应激和细胞凋亡水平升高。这些发现是否具有临床相关性尚需进一步研究。
