Toblli J E, Ferder L, Stella I, Angerosa M, Inserra F
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
J Urol. 2001 Jul;166(1):275-80.
Hyperoxaluria is a recognized cause of tubulointerstitial lesions and it may contribute to chronic renal failure. In previous studies we demonstrated that enalapril was effective against the progression of tubulointerstitial lesions in a 4-week hyperoxaluria rat model. We evaluated whether the action of enalapril on the tubulointerstitial lesions produced by hyperoxaluria persisted for a long period.
Two-month-old male Sprague-Dawley rats were divided into 4 groups of 12 each, including 1--control animals given tap water, 2--animals with hyperoxaluria, 3--animals with hyperoxaluria plus enalapril, 4--animals with enalapril. Hyperoxaluria in groups 2 and 3 rats was induced by administering 1% ethylene glycol, a precursor for oxalates, in the tap water continuously throughout the whole study. Meanwhile, groups 3 and 4 received 20 mg./l. enalapril in the drinking water. At the end of the study renal tubulointerstitial lesions were evaluated by immunostaining using monoclonal antibodies against macrophage infiltrates (ED1), tubulointerstitial alpha-smooth muscle actin and transforming growth factor-beta1. The lesions were quantified by semiquantitative scores. Creatinine clearance and urinary albumin excretion were also determined.
There was no difference in urine oxalate excretion in groups 2 and 3. Group 3 rats treated with enalapril showed fewer tubulointerstitial lesions than nontreated group 2 rats, as indicated by the mean scores plus or minus standard error of mean for inflammatory infiltrate (2.16 +/- 0.2 versus 0.83 +/- 0.16), tubular atrophy (2 +/- 0.27 versus 0.66 +/- 0.14), interstitial fibrosis (2.5 +/- 0.15 versus 0.5 +/- 0.1), glomerular ED1 (1.75 +/- 0.25 versus 0.16 +/- 0.11), interstitial ED1 (2.33 +/- 0.18 versus 0.58 +/- 0.10) tubular transforming growth factor-beta1 (2.09 +/- 0.08 versus 0.91 +/- 0.14), interstitial transforming growth factor-beta 1 (2.33 +/- 0.22 versus 0.66 +/- 0.12), tubulointerstitial alpha-smooth muscle actin (2.91 +/- 0.22 versus 0.83 +/- 0.16), lower urinary albumin excretion (35.5 +/- 2.7 mg. daily versus 10.9 +/- 1) and higher creatinine clearance (2.29 +/- 0.04 ml. per minute versus 2.54 +/- 0.03, all p <0.05).
Based on our results we believe that enalapril would provide a beneficial effect against chronic tubulointerstitial lesions caused by oxalates.
高草酸尿症是肾小管间质病变的一个公认病因，可能导致慢性肾衰竭。在先前的研究中，我们证明依那普利在为期4周的高草酸尿症大鼠模型中对肾小管间质病变的进展有效。我们评估了依那普利对高草酸尿症所致肾小管间质病变的作用是否能长期持续。
将2月龄雄性Sprague-Dawley大鼠分为4组，每组12只，包括：1组——给予自来水的对照动物；2组——高草酸尿症动物；3组——高草酸尿症加依那普利的动物；4组——依那普利动物。在整个研究过程中，持续给2组和3组大鼠饮用含1%乙二醇（草酸盐前体）的自来水以诱导高草酸尿症。同时，3组和4组在饮用水中加入20mg/L依那普利。研究结束时，使用针对巨噬细胞浸润（ED1）、肾小管间质α平滑肌肌动蛋白和转化生长因子-β1的单克隆抗体通过免疫染色评估肾小管间质病变。通过半定量评分对病变进行量化。还测定了肌酐清除率和尿白蛋白排泄量。
2组和3组的尿草酸排泄量无差异。用依那普利治疗的3组大鼠肾小管间质病变比未治疗的2组大鼠少，如炎症浸润（平均评分±平均标准误：2.16±0.2对0.83±0.16）、肾小管萎缩（2±0.27对0.66±0.14）、间质纤维化（2.5±0.15对0.5±0.1）、肾小球ED1（1.75±0.25对0.16±0.11）、间质ED1（2.33±0.18对0.58±0.10）、肾小管转化生长因子-β1（2.09±0.08对0.91±0.14）、间质转化生长因子-β1（2.33±0.22对0.66±0.12）、肾小管间质α平滑肌肌动蛋白（2.91±0.22对0.83±0.16）所示，尿白蛋白排泄量较低（每日35.5±2.7mg对10.9±1），肌酐清除率较高（每分钟2.29±0.04ml对2.54±0.03，均p<0.05）。
基于我们的研究结果，我们认为依那普利对草酸盐引起的慢性肾小管间质病变有益。
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