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高糖腹膜透析液所致大鼠腹膜的功能和结构改变及纤维化细胞因子的分泌

Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions.

作者信息

Liu Yang, Li Jian-Fei, Liu Hong, Liu Fu-You, Peng You-Ming, Liu Ying-Hong, Cheng Mei-Chu, Chen Guo-Chun, Zhou Xiang

机构信息

Division of Nephrology, Nephrology Institute of Central South University, 2nd Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Dialysis of Hunan Province , Changsha , China.

出版信息

Ren Fail. 2014 Mar;36(2):292-9. doi: 10.3109/0886022X.2013.844645. Epub 2013 Oct 24.

DOI:10.3109/0886022X.2013.844645
PMID:24152223
Abstract

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 β1 (TGF-β1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-β1, 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-β1, 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-β1, and FN proteins and the collagen thickness. The expression of TGF-β1 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-β1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.

摘要

目的

确定腹膜透析(PD)大鼠腹膜的功能和结构改变以及纤维化细胞因子的表达。

方法

将28只Sprague-Dawley(S-D)大鼠随机分为四组,每天用不同溶液进行透析,持续四周:(1)无溶液组(CON组),(2)0.9%生理盐水组(NS组),(3)1.5% Dianeal组(LG组),(4)4.25% Dianeal组(HG组)。测量腹膜平衡试验、超滤功能和流出液蛋白定量。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

给予4.25% Dianeal导致腹膜功能和结构改变,包括运输过程中的蛋白丢失、腹膜溶质转运率和超滤能力下降。HG组腹膜胶原比其他组厚。HG组CTGF、TGF-β1和FN蛋白水平显著最高,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表达显著高于其他组,且呈正相关。

结论

在大鼠中使用高糖腹膜透析液不仅可能导致腹膜纤维化,其由TGF-β1的异位表达促进,还会增加CTGF的表达。CTGF是PD大鼠腹膜纤维化的重要纤维化介质。

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