PS 04-30 THE EFFECT OF EPLERENONE ON CELL PROLIFERATION IN CONTRALATERAL KIDNEY OF RATS WITH UNILATERAL URETERAL OBSTRUCTION

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Abstract

Objective:

UUO model not only induces renal interstitial fibrosis(RIF) in obstructed kidney, but also induces injury in contralateral kidney. The precise mechanisms to induce RIF in the contralateral kidney are not well revealed. Proliferation appears early, even prior to the abnormal deposition of extracellular matrix, and continued throughout the whole process of fibrosis. We hypothesized that aldosterone may induce inflammation in the process of RIF in the contralateral kidney of UUO.

Design and Method:

36 female Wistar rats weight 200 ± 10g were used in this study. After 7 days to adapt, rats are randomly divided into 3 groups: Control group, UUO group, and UUO+Eplerenone group (100 mg/Kg/d). At the tenth day, they were sacrificed for further study.

Results:

1. In UUO group, the level of serum aldosterone, MCP-1 and TNF-α were increased significantly than sham group and they are lowered by Eplerenone. 2. Pathologic changes are determined by HE, MASSON and picrosirius red, PAS staining. The result showed that was no change in control group. In UUO group, renal interstitial fibrosis and inflammation cells were increased in the obstructed kidney. And severe inflammation also can be observed in the contralateral kidneys, which can be decreased by eplerenone. 3. Cell proliferation was examined by PCNA staining and PCNA positive cells increased markedly together with increased collagens in UUO group than control group in contralateral kidney and those changes are attenuated by Eplerenone. 4. The expression of SGK-1 protein and mRNA were upregulated in contralateral kidney in UUO group, which is suppressed by Eplerenone treatment. 5. NF-κB, ERK1/2 and P-ERK1/2 were also increased markedly in contralateral kidney of UUO than Sham group and downregulated after Eplerenone treatment.

Conclusions:

Aldosterone and its receptor (MR) activity are increased in contralateral kidney in obstructive nephropathy and they induce inflammation to stimulate cell proliferation via SGK-1/NF-kB/ERK pathway.

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