洛沙坦对阿霉素致大鼠慢性肾脏损害的长期保护作用

目的 :探讨洛沙坦对阿霉素肾病鼠慢性肾脏损害的长期保护作用及寻找一种研究肾素 血管紧张素系统(RAS)在肾脏慢性损害中的机制较为理想的动物模型。方法 :72只SD大鼠随机分为对照组、肾病组及干预组。分 2次 (间隔 2 0d)自其尾静脉注射阿霉素 (每次 2mg·kg- 1 )构建肾病慢性病理进展模型 ,洛沙坦 10mg (kg·d)灌胃进行干预。每 4周杀鼠一批观察大鼠肾脏重 体重比值、尿蛋白、血尿素氮、肌酐、白蛋白、胆固醇及肾脏病理。结果 :2 4h尿蛋白定量以肾病组为最高 ,对照组为最低 (P <0 .0 1) ;血尿素氮、血肌酐、肾脏重 体重比值、肾小球硬化评分及肾小管间质病理损害评分均以肾病组为最高 ,对照组为最低 (均P <0 .0 1)。结论 :洛沙坦能够长期减轻阿霉素肾病鼠的慢性肾脏损害 ;阿霉素肾病鼠是一种研究RAS导致肾损害的较为理想的动物模型。

Effect of losartan on the long-term renal protection of adriamycin-induced nephropathy rats

Objective To study the effect of losartan on the long term renal protection for adriamycin induced nephropathy rats and to provide an animal model for the study of renin angiotensin system induced chronic progressive kidney damage. Methods Seventy two rats were randomly divided into three groups(nephropathy, treated, and control groups). Adriamycin (2 mg·kg -1 ) was intravenously administered to the rats twice at a 20 day interval. The treated group received the angiotensin Ⅱ Type 1 specific receptor antagonist losartan [10 mg/(kg·d)] by gastric perfusion every day. Animals were killed every 4 weeks. Blood biochemical analyses (creatinine, urea nitrogen, albumin, and cholesterol), 24 h urinary protein, the ratio of kidney weight to body weight and pathologic histologic injures were checked. Results The 24 h urinary protein excretion was the largest in the nephropathy rats, and the smallest in the control rats at each time point during the experiment (P<0.01). Concentrations of blood urea nitrogen and serum creatinine, the ratio of kidney weight to body weight, score of glomerular sclerosis and tubulointerstitial pathologic lesions were the highest in the nephropathy rats and the lowest in the control rats (P<0.01). Conclusion Losartan can reduce chronic progressive kidney lesions in a long term. Adriamycin nephropathy rats are ideal animal models to study the mechanism of kidney lesions.