아드리아마이신으로 유발된 마우스 신부전 모델에서 로자탄의 효과
Effect of Losartan on Adriamycin induced nephropathy rat model
Abstract
Purpose: Adriamycin (ADR) nephropathy is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Data from animal models suggest that blockade of angiotensin (AT) II by angiotensin-converting enzyme (ACE) inhibitor, or AT receptor blocker (ARB) not only induces intraglomerular hemodynamic changes that favor reduction of glomerular protein ultrafiltration, but also attenuates inflammatory cell infiltration into the kidney. The purpose of this study was to investigate the preventive effect of losartan in ADR induced nephropathy rat model. Methods: Sprague-Dawley male rats were divided into three groups. All three groups were given intraperitoneal injections once a week for 3 weeks: control group (0.9% normal saline), ADR group (ADR 5 mg/kg), losartan group was treated with ADR (5 mg/kg) and losartan (10 mg/kg/day). Urine was collected before and after injection weekly for 3 weeks, The rats were sacrificed at week 3. Endothelin (ET)-1, AT II receptor type 1A, ACE, Interleukin (IL)-6, tumor necrosis factor (TNF)-α and caspase-3 protein expressions were estimated by western blot analysis. Results; At week 3 after ADR injection, serum creatinine showed significant increase in ADR group (1.79±0.43 mg/dl) compared to control (0.58±0.05 mg/dl). In losartan group, creatinine level was significantly lower (0.91±0.06 mg/dl) compared to ADR group ( P0.05). On the other hand, albumin and lipid profiles were not significant different between the three groups. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule (KIM-1), proteinuria and microalbuminuria in ADR group showed continuous and significant increase every week compared to control group. Losartan group showed significant reduction compared to ADR group. Protein expressions of TNF-α. AT II receptor type 1A, ACE, ET-1 and caspase-3 in the kidney tissues were significantly increased in ADR group. They were significantly reduced after losartan treatment. Histological examinations of kidney demonstrated that glomerular and tubulointerstitial damage including glomerulosclerosis was significantly increased in ADR group. In contrast, losartan group significantly ameliorated severe damage lesions of glomerulosclerosis. Conclusion: We demonstrated that losartan has a renoprotective effect in ADR induced nephropathy.