Nakhoul Farid, Khankin Eliyahu, Yaccob Afif, Kawachi Hiroshi, Karram Tony, Awaad Huda, Nakhoul Nakhoul, Hoffman Aaron, Abassi Zaid
Ambulatory Nephrology Unit, Rambam-Health Care Campus, Faculty of Medicine, Technion, Haifa 31096, Israel.
Am J Physiol Renal Physiol. 2008 Mar;294(3):F628-37. doi: 10.1152/ajprenal.00524.2007. Epub 2007 Dec 19.
Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and edema. It is believed that nephrin and podocin are involved in the development of proteinuria. The proteinuria and effects of eplerenone alone or combined with enalapril on nephrin/podocin abundance in rats with NS have not yet been studied. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of eplerenone and enalapril, alone or combined, on proteinuria and nephrin/podocin abundance in rats with adriamycin-induced NS. Adriamycin caused a significant increase in daily protein excretion (U(pr)V; from 26.96 +/- 3.43 to 958.57 +/- 56.7 mg/day, P < 0.001) and cumulative proteinuria [from 900.33 +/- 135.5 to 22,490.62 +/- 931.26 mg (P < 0.001)] during 6 wk. Early treatment with enalapril significantly decreased U(pr)V from 958.6 +/- 56.7 to 600.31 +/- 65.13 mg/day (P < 0.001) and cumulative proteinuria to 12,842.37 +/- 1,798.17 mg/6 wk (P < 0.001). Similarly, early treatment with eplerenone produced a profound antiproteinuric effect: U(pr)V decreased from 958.57 +/- 56.7 to 593.38 +/- 21.83 mg/day, P < 0.001, and cumulative proteinuria to 16,601.84 +/- 1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when enalapril and eplerenone were combined: U(pr)V decreased from 958.57 +/- 56.69 to 424.17 +/- 38.54 mg/day, P < 0.001, and cumulative protein excretion declined to 10,252.88 +/- 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular nephrin and podocin. In contrast, late treatment with either enalapril or eplerenone alone or combined mildly decreased U(pr)V and cumulative proteinuria. Thus pretreatment with eplerenone or enalapril is effective in reducing daily and cumulative protein excretion and preservation of nephrin/podocin. More profound antiproteinuric effects were obtained when enalapril and eplerenone were combined.
肾病综合征（NS）是一种以大量蛋白尿和水肿为特征的临床状态。据信，nephrin和足突蛋白参与蛋白尿的发生发展。依普利酮单独或与依那普利联合使用对NS大鼠nephrin/足突蛋白丰度的蛋白尿及影响尚未得到研究。因此，本研究旨在考察依普利酮和依那普利单独或联合使用对阿霉素诱导的NS大鼠蛋白尿及nephrin/足突蛋白丰度的早期（NS诱导前2天开始）和晚期（NS诱导后2周开始）影响。阿霉素导致6周内每日尿蛋白排泄量（U(pr)V；从26.96±3.43增至958.57±56.7mg/天，P<0.001）和累积蛋白尿[从900.33±135.5增至22,490.62±931.26mg（P<0.001）]显著增加。依那普利早期治疗使U(pr)V从958.6±56.7显著降至600.31±65.13mg/天（P<0.001），累积蛋白尿降至12,842.37±1,798.17mg/6周（P<0.001）。同样，依普利酮早期治疗产生了显著的抗蛋白尿作用：U(pr)V从958.57±56.7降至593.38±21.83mg/天，P<0.001，累积蛋白尿降至16,601.84±1,334.31mg/6周；P<0.001。依那普利和依普利酮联合使用时获得了相加效应：U(pr)V从958.57±56.69降至424.17±38.54mg/天，P<0.001，累积尿蛋白排泄量降至10,252.88±1,011.3mg/6周，P<0.001。这些抗蛋白尿作用与肾小球nephrin和足突蛋白的大量保留有关。相比之下,依那普利或依普利酮单独或联合晚期治疗使U(pr)V和累积蛋白尿轻度降低。因此，依普利酮或依那普利预处理可有效减少每日和累积尿蛋白排泄并保留nephrin/足突蛋白。依那普利和依普利酮联合使用时获得了更显著的抗蛋白尿作用。
