Nephrology, Nagoya University Graduate School of Medicine , Nagoya , Japan.
Renal Replacement Therapy, Nagoya University Graduate School of Medicine , Nagoya , Japan.
Am J Physiol Renal Physiol. 2018 Dec 1;315(6):F1732-F1746. doi: 10.1152/ajprenal.00172.2018. Epub 2018 Oct 3.
In a previous study of fungal peritoneal injury in peritoneal dialysis patients, complement (C)-dependent pathological changes were developed in zymosan (Zy)-induced peritonitis by peritoneal scraping. However, the injuries were limited to the parietal peritoneum and did not show any fibrous encapsulation of the visceral peritoneum, which differs from human encapsular peritoneal sclerosis (EPS). We investigated peritoneal injury in a rat model of Zy-induced peritonitis pretreated with methylglyoxal (MGO) instead of scraping (Zy/MGO peritonitis) to clarify the role of C in the process of fibrous encapsulation of the visceral peritoneum. Therapeutic effects of an anti-C5a complementary peptide, AcPepA, on peritonitis were also studied. In Zy/MGO peritonitis, peritoneal thickness, fibrin exudation, accumulation of inflammatory cells, and deposition of C3b and C5b-9 with loss of membrane C regulators were increased along the peritoneum until day 5. On day 14, fibrous encapsulation of the visceral peritoneum was observed, resembling human EPS. Peritoneal injuries and fibrous changes were significantly improved with AcPepA treatment, even when AcPepA was administered following injection of Zy in Zy/MGO peritonitis. The data show that C5a might play a role in the development of encapsulation-like changes in the visceral peritoneum in Zy/MGO peritonitis. AcPepA might have therapeutic effects in fungal infection-induced peritoneal injury by preventing subsequent development of peritoneal encapsulation.
在之前一项研究真菌性腹膜损伤的腹膜透析患者中，补体（C）依赖的病理性变化是在酵母聚糖（Zy）诱导的腹膜炎中通过腹膜刮除发展的。然而，损伤仅限于壁层腹膜，没有任何内脏腹膜的纤维包裹，这与人类包裹性腹膜硬化症（EPS）不同。我们研究了酵母聚糖（Zy）预处理诱导腹膜炎的大鼠模型中的腹膜损伤，而不是刮除（Zy/MGO 腹膜炎），以阐明 C 在纤维包裹内脏腹膜过程中的作用。我们还研究了一种抗 C5a 互补肽 AcPepA 对腹膜炎的治疗效果。在 Zy/MGO 腹膜炎中，腹膜厚度、纤维蛋白渗出、炎症细胞积聚以及 C3b 和 C5b-9 的沉积（伴有膜 C 调节剂的丢失）沿着腹膜增加，直到第 5 天。第 14 天，观察到内脏腹膜的纤维包裹，类似于人类 EPS。用 AcPepA 治疗后，腹膜损伤和纤维变化显著改善，即使在 Zy/MGO 腹膜炎中在注射 Zy 后给予 AcPepA 也是如此。这些数据表明 C5a 可能在 Zy/MGO 腹膜炎中内脏腹膜包裹样变化的发展中起作用。AcPepA 通过防止随后发生的腹膜包裹，可能对真菌感染诱导的腹膜损伤具有治疗作用。
