Hirata Haruna, Miyamoto Hirotaka, Shimokawa Kenta, Nakashima Mikiro, Nakayama Morio, Fumoto Shintaro, Nishida Koyo
Graduate School of Biomedical Sciences, Nagasaki University.
Biol Pharm Bull. 2014;37(2):262-7. doi: 10.1248/bpb.b13-00730.
Long-term peritoneal dialysis (PD) frequently produces morphological and functional changes of the peritoneum, which makes continuation of PD difficult. Moreover, the progression of peritoneal injury causes complications and poor prognosis. Since therapeutic treatments for peritoneal injury during PD have yet to be established, it is important to diagnose peritoneal injury as early as possible. The aim of this study was to develop a method of monitoring peritoneal function to diagnose peritoneal injury. Model rats of peritoneal injury were prepared by intraperitoneal injection of methylglyoxal (MGO) for five consecutive days. Then, marker substances of various molecular weights (phenolsulfonphthalein, fluorescein isothiocyanate-dextran (FD)-10, FD-40, FD-70, FD-2000 or tetramethylrhodamine-dextran (RD)-10) were injected into the peritoneal cavity. At 120 min after injection, the remaining amounts of all marker substances were significantly decreased in the MGO-treated rats compared with those in the vehicle-treated rats. Molecular weight dependence of the peritoneal permeability was observed. A substance with a molecular weight of approximately 10000 was found to be suitable to diagnose peritoneal injury. Moreover, coadministration of RD-10 with FD-2000 enabled us to monitor enhanced peritoneal permeability and the transfer of water simultaneously, without the recovery of whole PD fluid, even in the case of different ultrafiltration volumes. We demonstrated the usefulness of administering substances to evaluate peritoneal permeability and the transfer of water simultaneously to diagnose peritoneal injury. This study should be valuable for safe and effective PD.
长期腹膜透析(PD)常导致腹膜出现形态和功能变化,这使得PD的持续进行变得困难。此外,腹膜损伤的进展会引发并发症并导致预后不良。由于PD期间腹膜损伤的治疗方法尚未确立,尽早诊断腹膜损伤很重要。本研究的目的是开发一种监测腹膜功能以诊断腹膜损伤的方法。通过连续五天腹腔注射甲基乙二醛(MGO)制备腹膜损伤模型大鼠。然后,将各种分子量的标记物质(酚红、异硫氰酸荧光素 - 葡聚糖(FD)-10、FD - 40、FD - 70、FD - 2000或四甲基罗丹明 - 葡聚糖(RD)-10)注入腹腔。注射后120分钟时,与溶剂处理组大鼠相比,MGO处理组大鼠中所有标记物质的剩余量均显著降低。观察到腹膜通透性与分子量的相关性。发现分子量约为10000的物质适合用于诊断腹膜损伤。此外,RD - 10与FD - 2000联合给药使我们能够同时监测增强的腹膜通透性和水的转运,即使在超滤量不同的情况下,也无需回收全部PD液。我们证明了同时给予物质以评估腹膜通透性和水的转运来诊断腹膜损伤的有效性。本研究对于安全有效的腹膜透析应具有重要价值。