Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions
Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions
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DOI：
10.3109/0886022x.2013.844645
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发表时间：
2014-03-01
期刊：
影响因子：
3
通讯作者：
Zhou, Xiang
中科院分区：
文献类型：
--
作者：
Liu, Yang;Li, Jian-Fei;Zhou, Xiang
目的：确定腹膜透析（PD）大鼠腹膜的功能和结构变化以及纤维化细胞因子的表达。方法：28只Sprague-Dawley（S-D）大鼠随机分为4组，每天用不同溶液透析4周：（1）无溶液（CON组），（2）0.9%生理盐水（NS组），（3）1.5% Dianeal（LG组），（4）4.25% Dianeal（HG组）。测量腹膜平衡测试、超滤功能和流出物蛋白质定量。研究腹膜形态并进行免疫组织化学检测转化生长因子β1（TGF-β1）、结缔组织生长因子（CTGF）和纤连蛋白（FN）蛋白。采用逆转录聚合酶链反应分析TGF-β1、CTGF mRNA的表达。结果：4.25% Dianeal 给药引起腹膜功能和结构变化，包括转运过程中蛋白质损失、腹膜溶质转运速率和超滤能力降低。 HG组腹膜胶原较其他组厚。 HG组的CTGF、TGF-β1和FN蛋白水平显着最高，其次是LG组。线性相关分析显示CTGF、TGF-β1和FN蛋白水平与胶原厚度呈正相关。 HG组TGF-β1和CTGF mRNA的表达量显着高于其他组，且呈正相关。结论：大鼠使用高糖腹膜透析液不仅可能导致TGF-β1异位表达促进腹膜纤维化的进展，而且可能增加CTGF的表达。 CTGF是PD大鼠腹膜纤维化的重要纤维化介质。
Objective: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. Methods: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor beta 1 (TGF-beta 1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-beta 1, CTGF mRNA. Results: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-beta 1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-beta 1, and FN proteins and the collagen thickness. The expression of TGF-beta 1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation. Conclusion: Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-beta 1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.