Peritoneal Injury by Methylglyoxal in Peritoneal Dialysis
Peritoneal Injury by Methylglyoxal in Peritoneal Dialysis
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DOI：
10.1177/089686080602600317
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发表时间：
2006-05
影响因子：
2.8
通讯作者：
I. Hirahara;E. Kusano;S. Yanagiba;Yukio Miyata;Y. Ando;S. Muto;Y. Asano
中科院分区：
文献类型：
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作者：
I. Hirahara;E. Kusano;S. Yanagiba;Yukio Miyata;Y. Ando;S. Muto;Y. Asano
背景腹膜透析（PD）是肾功能减退或缺失患者的常见治疗方法。长期腹膜透析导致腹膜损伤，结构改变和功能下降，如超滤丧失。在最坏的情况下，腹膜损伤导致包裹性腹膜硬化，这是PD的严重并发症。PD液中含有的葡萄糖降解产物导致常规PD液的生物不相容性。甲基乙二醛（MGO）是一种毒性极强的葡萄糖降解产物。本研究探讨了MGO对腹膜的损伤作用。方法雄性Sprague-Dawley大鼠（n = 6），连续21 d，每天灌胃含0、0.66、2、6.6、20 mmol/L MGO的PD液（pH 5.0）。在第22天，通过腹膜平衡试验评估腹膜功能。分析引流的透析液的IV型胶原蛋白-7S、基质金属蛋白酶（MMP）和血管内皮生长因子（VEGF）。还进行了组织学分析。结果MGO浓度超过0.66mmol/L时，大鼠腹膜功能明显下降，引流液中Ⅳ型胶原7S和MMP-2水平明显升高。在20 mmol/L的MGO处理的大鼠中，体重减轻，VEGF的表达，腹膜增厚，并形成腹茧。MMP-2和VEGF由腹膜中的浸润细胞产生。微血管基底膜可见IV型胶原。结论MGO不仅可引起腹膜损伤，而且可引起在体腹茧形成。腹膜功能的下降可能与微血管基底膜的重建或新生血管的形成有关。
Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats (n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.