Song Sang Heon, Kwak Ihm Soo, Yang Byeong Yun, Lee Dong Won, Lee Soo Bong, Lee Min Young
Department of Internal Medicine, Pusan National University Hospital, Ami-dong, Seo-gu, Busan, Korea.
Nephrology (Carlton). 2009 Apr;14(2):155-63. doi: 10.1111/j.1440-1797.2008.01037.x.
The aim of this study was to demonstrate the efficacy of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist, rosiglitazone, in the amelioration or prevention of inflammation including peritoneal fibrosis secondary to the peritonitis in a peritoneal dialysis (PD) model of non-uraemic rats.
Thirty male Sprague-Dawley rats were assigned to six groups according to treatment. A 90 min peritoneal equilibrium test, dialysate cellular components, peritoneal thickness and cellularity were assessed on day 21. Additionally, immunohistochemical stains of peritoneal membrane, such as PPAR-gamma, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, collagen-1 and monocyte chemoattractant protein-1 were performed.
The dialysate neutrophil count and peritoneal thickness in the high-dose rosiglitazone group was significantly decreased compared to the lipopolysaccharide (LPS)-only group. The peritoneal membrane from the LPS-only group showed marked cellular proliferation in the area of the submesothelial compact zone compared with the PD-only group, the rosiglitazone-only group, and the high-dose rosiglitazone group. The 90 min peritoneal equilibrium test (PET) results showed no statistical difference among the six groups excluding dialysate-to-plasma urea ratio. The number of PPAR-gamma expressing cells and the expression of TGF-beta1 were decreased in the high-dose rosiglitazone group compared to the LPS-only group. There were no differences in the expression of VEGF and collagen-1 among the six groups. Interestingly, the number of PPAR-gamma-positive cells was correlated with expression of VEGF, TGF-beta1, collagen-1 and monocyte chemoattractant protein-1 irrespective of the study group.
The results of this study showed that rosiglitazone ameliorated peritoneal inflammation induced by LPS and reduced the TGF-beta1 expression in the peritoneal membranes.
本研究旨在证明过氧化物酶体增殖物激活受体（PPAR）-γ激动剂罗格列酮在改善或预防非尿毒症大鼠腹膜透析（PD）模型中包括腹膜炎继发腹膜纤维化在内的炎症方面的疗效。
30只雄性Sprague-Dawley大鼠按治疗方法分为6组。在第21天评估90分钟腹膜平衡试验、透析液细胞成分、腹膜厚度和细胞密度。此外，对腹膜进行免疫组织化学染色，检测PPAR-γ、血管内皮生长因子（VEGF）、转化生长因子（TGF）-β1、胶原蛋白-1和单核细胞趋化蛋白-1等。
与仅用脂多糖（LPS）组相比，高剂量罗格列酮组的透析液中性粒细胞计数和腹膜厚度显著降低。与仅行PD组、仅用罗格列酮组和高剂量罗格列酮组相比，仅用LPS组的腹膜间皮下致密区出现明显的细胞增殖。90分钟腹膜平衡试验（PET）结果显示，除透析液与血浆尿素比值外，6组之间无统计学差异。与仅用LPS组相比，高剂量罗格列酮组PPAR-γ表达细胞数量和TGF-β1表达降低。6组之间VEGF和胶原蛋白-1的表达无差异。有趣的是，无论研究组如何，PPAR-γ阳性细胞数量与VEGF、TGF-β1、胶原蛋白-1和单核细胞趋化蛋白-1的表达均相关。
本研究结果表明，罗格列酮可改善LPS诱导的腹膜炎症，并降低腹膜中TGF-β1的表达。
