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논문분류	춘계학술대회 초록집
제목	Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-induced Diabetic Nephropathy
저자	Hua Jin, Shang Guo Piao, Jian Jin, Can Li
출판정보	2014; 2014(1):
키워드	Leflunomide, Benazepril, Diabetic nephropathy, MCP-1
초록	Background/Aims: Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. Methods: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10mg/kg), benazepril (10 mg/ kg), or a combination of LEF and benazepril. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory (monocyte chemoattractant protein-1 [MCP-1] and Toll-like receptor-2 [TLR-2]) and glomerulosclerotic factors (Transforming growth factor-beta1 [TGF-β1] and connective tissue growth factor [CTGF]), and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. Results: Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p<0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β1 and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p<0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. Conclusion: LEF treatment lessens DN, and combined treatment with LEF and benazepril provided synergistic effects in preventing DN.
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