Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

نویسندگان

  • Sang-Youb Han
  • Cy-Hyun Kim
  • Han-Seong Kim
  • Yi-Hwa Jee
  • Hye-Kyoung Song
  • Mi-Hwa Lee
  • Kum-Hyun Han
  • Hyoung-Kyu Kim
  • Young-Sun Kang
  • Jee-Young Han
  • Young-Sik Kim
  • Dae-Ryong Cha
چکیده

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and proximal tubular cells. There were no changes in blood glucose concentration or BP after spironolactone treatment. Spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of MCP-1 were significantly increased concurrently with renal expression of MCP-1, macrophage migration inhibitory factor, and macrophage infiltration. Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as well as renal MCP-1 and migration inhibitory factor expression and macrophage infiltration. In addition, aldosterone induced upregulation of MCP-1 expression and NF-kappaB transcriptional activity in cultured cells, and spironolactone reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB inhibition abolished aldosterone-induced MCP-1 production. Overall, these findings suggest that aldosterone-induced NF-kappaB activation leads to activation of proinflammatory cytokines, ultimately leading to renal injury in this model. These data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy.

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عنوان ژورنال:
  • Journal of the American Society of Nephrology : JASN

دوره 17 5  شماره 

صفحات  -

تاریخ انتشار 2006