Korean Journal of Nephrology 2007;26(5):526-533.
Combination Treatment with Retinoid and Peroxisome Proliferator-Activated Receptors (PPAR)-γ Agonist on Streptozotocin-Induced Diabetic Nephropathy
Sang-Youb Han, M.D.1, 2, Cy-Hyun Kim, M.D.2, Kum-Hyun Han, M.D.1 Dae-Ryong Cha, M.D.3 and Han-Seong Kim, M.D.4
Department of Internal Medicine1
Clinical Research Center, Ilsan-Paik Hospital2 Department of Pathology4
Inje University, Department of Internal Medicine, Korea University3
당뇨병성 신증쥐에서 retinoid와 PPAR-γ 촉진제 병합투여에 관한 연구
한상엽1, 2 김시현2 한금현1 차대룡3 김한성4
인제의대 내과학교실1, 인제의대 일산백병원 임상연구센터2, 고려의대 내과학교실3, 인제의대 병리학교실4
Abstract
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.
Key Words: Retinoids, Peroxisome proliferator-activated receptors, Diabetic nephropathies, Inflammation
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