Department of Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Nephrol Dial Transplant. 2012 Feb;27(2):526-36. doi: 10.1093/ndt/gfr302. Epub 2011 Jun 9.
Atrial natriuretic peptide (ANP) was recently reported to ameliorate fibrosis in the heart and experimental renal diseases and vascular thickening after balloon injury. Peritoneal fibrosis is an important complication of long-term peritoneal dialysis, and peritonitis is a factor in its onset. In the present study, we investigated the effects of ANP in a rat peritonitis-induced peritoneal fibrosis model.
As pretreatment, an osmotic pump containing vehicle (saline) or ANP (0.15 or 0.3 μg/min) was inserted through the carotid vein in male Sprague-Dawley rats. ANP or saline was continuously infused using the osmotic pump. Three days after administration of ANP or saline, rats underwent peritoneal scraping in a blind manner and were sacrificed on Day 14. The effects of ANP were evaluated based on peritoneal thickness, immunohistochemistry and real-time polymerase chain reaction. In each experiment, we evaluated messenger RNA (mRNA) expression of the ANP receptor natriuretic peptide receptor A (NPR-A) in the peritoneum after scraping. The effects of ANP were also studied in cultured peritoneal fibroblasts and mesothelial cells.
We observed a significant increase in NPR-A mRNA in the peritoneum. Peritoneal thickness increased with time and peaked on Day 14, but ANP significantly reduced peritoneal thickness. Parameters such as number of macrophages and CD-31-positive vessels and expression of type III collagen/transforming growth factor-β/plasminogen activator inhibitor-1 (PAI-1)/connective tissue growth factor (CTGF) were significantly suppressed by ANP. In cultured peritoneal fibroblasts and mesothelial cells, ANP suppressed angiotensin II-induced upregulation of CTGF and PAI-1.
Our results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis.
心房利钠肽 (ANP) 最近被报道可改善心脏纤维化和实验性肾病以及球囊损伤后的血管增厚。腹膜纤维化是长期腹膜透析的一个重要并发症，腹膜炎是其发病的一个因素。在本研究中，我们研究了 ANP 在大鼠腹膜炎诱导的腹膜纤维化模型中的作用。
作为预处理，通过颈静脉插入含有载体（盐水）或 ANP（0.15 或 0.3μg/min）的渗透泵。使用渗透泵持续输注 ANP 或盐水。在给予 ANP 或盐水 3 天后，大鼠进行盲法腹膜刮除，并在第 14 天处死。根据腹膜厚度、免疫组织化学和实时聚合酶链反应评估 ANP 的作用。在每个实验中，我们评估了刮除后腹膜中 ANP 受体利钠肽受体 A（NPR-A）的信使 RNA（mRNA）表达。还研究了 ANP 在培养的腹膜成纤维细胞和间皮细胞中的作用。
我们观察到腹膜中 NPR-A mRNA 表达显著增加。腹膜厚度随时间增加，并在第 14 天达到峰值，但 ANP 显著降低了腹膜厚度。巨噬细胞数量和 CD-31 阳性血管以及 III 型胶原/转化生长因子-β/纤溶酶原激活物抑制剂-1（PAI-1）/结缔组织生长因子（CTGF）的表达等参数均被 ANP 显著抑制。在培养的腹膜成纤维细胞和间皮细胞中，ANP 抑制了血管紧张素 II 诱导的 CTGF 和 PAI-1 的上调。
我们的结果表明，ANP 可用于预防炎症诱导的腹膜纤维化。
