N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

被引：49

作者：

Wang, Mingao ^{[1
]}

Liu, Ruichan ^{[1
]}

Jia, Xibei ^{[1
]}

Mu, Suhong ^{[1
]}

Xie, Rujuan ^{[1
]}

机构：

[1] Harbin Med Coll, Dept Nephrol, Affiliated Hosp 1, Harbin 150001, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2010年 / 26卷 / 06期

关键词：

N-acetyl-seryl-aspartyl-lysyl-proline; monocyte chemoattractant protein-1; nuclear factor-kappa B; alpha-smooth muscle actin; transforming growth factor-beta 1; FACTOR-KAPPA-B; GROWTH-FACTOR-BETA; CHEMOATTRACTANT PROTEIN-1 EXPRESSION; TUBULAR EPITHELIAL-CELLS; ANGIOTENSIN-II; OBSTRUCTIVE NEPHROPATHY; MESENCHYMAL TRANSITION; INTERSTITIAL FIBROSIS; URETERAL OBSTRUCTION; TISSUE FIBROSIS;

D O I：

10.3892/ijmm_00000527

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

It has been reported that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) attenuates renal and cardiac inflammation as well as fibrosis in hypertensive rats. In this study, we investigated these effects using a unilateral ureteral obstruction (UUO) model. Eighteen male Wistar rats were randomly divided into three groups: control, UUO/vehicle and UUO/Ac-SDKP groups. Animal models of renal inflammation and tubulointerstitial fibrosis were established with unilateral ureteral ligation in rats. Ac-SDKP and vehicle were infused subcutaneously by using osmotic mini pumps for two weeks. On the 14th day post-injection, kidney histological changes of each group were observed by hematoxylin-eosin and Masson's stain. Renal macrophage infiltration, together with protein expression and localization of monocyte chemoattractant protein-1 (MCP-1), nuclear factor-kappa B (NF-kappa B), alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF-beta 1) in renal tissue was assessed by immunohistochemical staining. Gene expression of MCP-1 and TGF-beta 1 was analyzed with reverse transcription-polymerase chain reaction. Ac-SDKP-treated animals demonstrated less severe renal inflammation and tubulointerstitial fibrosis. Interstitial fibrosis was significantly attenuated with Ac-SDKP. ED-1 was expressed in the interstitium of the UUO/vehicle group kidneys and decreased with Ac-SDKP treatment. MCP-1, NE-kappa B, alpha-SMA and TGF-beta 1 were increased in the renal interstitium and tubular epithelial cells of the UUO/vehicle group. Ac-SDKP significantly reduced their expressions. Gene expressions of MCP-1 and TGF-beta 1 were upregulated in the UUO/vehicle group kidneys and were significantly inhibited by Ac-SDKP. In conclusion, in the rat UUO model Ac-SDKP administration protected against renal inflammation and tubulointerstitial fibrosis. The inhibitory effect of Ac-SDKP was mediated by the reduction in the expression of MCP-1, NF-kappa B, alpha-SMA and TGF-beta 1.

引用

页码：795 / 801

页数：7

共 36 条

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