Novel Diagnostic Method of Peritoneal Injury Using Dual Macromolecular Markers

Novel Diagnostic Method of Peritoneal Injury Using Dual Macromolecular Markers
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DOI:
10.1248/bpb.b13-00730
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发表时间:
2014-02-01
影响因子:
2
通讯作者:
Nishida, Koyo
Nishida, Koyo
中科院分区:
医学4区
文献类型:
--
作者:
Hirata, Haruna;Miyamoto, Hirotaka;Nishida, Koyo

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长期腹膜透析(PD)经常引起腹膜的形态和功能改变,使PD的持续困难。此外,腹膜损伤的进展会导致并发症和预后不良。由于PD期间腹膜损伤的治疗方法尚未建立,因此尽早诊断腹膜损伤非常重要。本研究的目的是建立一种监测腹膜功能的方法来诊断腹膜损伤。连续5天腹腔注射甲基乙二醛(MGO)制备腹膜损伤模型大鼠。然后腹腔注射不同分子量的标记物(苯酚磺酞、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)。注射后120mm, mgo处理的大鼠体内所有标记物质残留量均明显低于载药处理的大鼠。观察腹腔通透性的分子量依赖性。发现一种分子量约为10000的物质适合诊断腹膜损伤。此外,RD-10与FD-2000联合给药使我们能够同时监测腹膜通透性增强和水的转移,即使在不同超滤体积的情况下,也不会恢复整个PD液。我们证明了给药评估腹膜通透性和水转移同时诊断腹膜损伤的有效性。本研究对安全有效的PD治疗具有一定的参考价值。
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 mm 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.