당뇨병성 신증쥐에서 retinoid와 PPAR-γ 촉진제 병합투여에 관한 연구

초록

Purpose : An inflammatory mechanism has been suggested to contribute to the progression of diabetic nephropathy. Both retinoid and PPAR-γ agonist, known anti-inflammatory agents, have been reported to be beneficial in diabetic nephropathy. Because they form heterodimer for transcription within the nucleus, we investigated the effect of a combination treatment with them in streptozotocin (STZ)-induced diabetic rats. Methods : STZ-induced diabetic rats were treated with retinoid and PPAR-γ agonist. The effects were determined by measuring urinary monocyte chemoattractant peptide (MCP)-1, proteinuria, and intrarenal ED-1 expression. Results : Blood glucose concentration was higher in diabetic rats than in control rats. Retinoid and PPAR-γ agonist did not affect blood glucose concentration. Urinary protein excretion (8.6±0.69 vs. 22.1 mg/mgCr, p<0.01) and urinary MCP-1 (19.8±3.4 vs. 61.5±6.1 pg/mgCr, p<0.01) were significantly higher in diabetic rats at four weeks after the induction of diabetes compared with controls. Proteinuria in the group with retinoic acid (16.9±1.4, mg/mgCr, p<0.05) and PPAR-γ agonist (14.6±1.5 mg/mgCr, p<0.05) were decreased. Retinoic acid (42.2±2.7 pg/mgCr, p<0.05) and PPAR-γ agonist (40.5±pg/mgCr, p<0.05) significantly suppressed MCP-1 level in diabetic rats. However, combination treatment was not effective to proteinuria and urinary MCP-1 concentration. Urinary protein excretion was significantly correlated with MCP-1 (r=0.9, p<0.01). Immunohistochemistry revealed a significant increase in staining for ED-1 protein in the diabetic kidneys. Both retinoid and PPAR-γ agonist significantly suppressed intrarenal ED-1 synthesis. However combination treatment didn't show any additional beneficial effects. Conclusion : Both retinoic acid and PPAR-γ agonist suppressed proteinuria and inflammatory changes in diabetic rats. However, there were no additional effects of the combination treatment present. Further research is needed to determine the effect of the combination treatment on diabetic nephropathy.

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