Department of Nephrology, Huadu District People's Hospital, Southern Medical University, 22# Baohua Road, Huadu District, Guangzhou 510800, China.
Department of Nephrology, Huadu District People's Hospital, Southern Medical University, 22# Baohua Road, Huadu District, Guangzhou 510800, China
Biosci Rep. 2018 Jun 21;38(3). doi: 10.1042/BSR20180009. Print 2018 Jun 29.
Peritonitis is still a major cause of the death in peritoneal dialysis (PD) patients despite the significant decline of the peritonitis rates in recent years. The present study is designed to evaluate the therapeutic potential of peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on the structure and function of the peritoneum in a PD rat accompanied with peritonitis induced by lipopolysaccharide (LPS). Our data showed that the peritoneal membrane in the LPS-only group showed increased peritoneal thickness, vessel density, and hypercellularity compared with the PD-only group. Rosiglitazone administration significantly inhibited increase of the three indicators in PD rats with LPS treatment. In line with this, rosiglitazone improved function of the peritoneum in LPS-induced PD rats receiving rosiglitazone, which was reflected by decreased D/P urea and D/P albumin. Mechanistically, rosiglitazone-mediated improvements in the damaged structure and function of the peritoneum in PD rats with LPS treatment were associated with reduced inflammation and preserving mesothelial cell monolayer resulted from up-regulation of AQP-1 and ZO-1. Our findings thus suggest that peroxisome proliferator-activated receptor γ (PPAR-γ) activation might be a reasonable strategy to prevent and ameliorate peritoneal deterioration in PD patients, especially with peritonitis.
腹膜炎仍然是腹膜透析（PD）患者死亡的主要原因，尽管近年来腹膜炎发生率显著下降。本研究旨在评估过氧化物酶体增殖物激活受体-γ 激动剂罗格列酮对脂多糖（LPS）诱导腹膜炎的 PD 大鼠腹膜结构和功能的治疗潜力。我们的数据表明，与 PD 组相比，LPS 组的腹膜厚度、血管密度和细胞密度增加。罗格列酮给药可显著抑制 LPS 处理 PD 大鼠这三个指标的增加。与此一致的是，罗格列酮改善了 LPS 诱导的 PD 大鼠的腹膜功能，这反映在 D/P 尿素和 D/P 白蛋白的减少。从机制上讲，罗格列酮介导的 LPS 处理 PD 大鼠受损腹膜结构和功能的改善与炎症减轻和间皮细胞单层的维持有关，这是由 AQP-1 和 ZO-1 的上调引起的。因此，我们的研究结果表明，过氧化物酶体增殖物激活受体γ（PPAR-γ）的激活可能是预防和改善 PD 患者，特别是腹膜炎患者腹膜恶化的合理策略。
