Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-thy-1 irreversible nephritis
Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-thy-1 irreversible nephritis
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DOI：
10.1291/hypres.27.971
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Saruta, T
中科院分区：
文献类型：
--
作者：
Asai, M;Monkawa, T;Saruta, T
阻断肾素-血管紧张素系统已被确立为治疗心力衰竭伴高血压和左心室肥大以及进行性肾脏疾病的方法。本研究的目的是探讨是否螺内酯，盐皮质激素受体拮抗剂，单独或与西拉普利，血管紧张素转换酶（ACE）抑制剂，改善蛋白尿和肾脏病变的免疫启动进行性肾炎模型。在注射抗Thy-1单克隆抗体1-22-3以诱导进行性肾小球肾炎之前7天，将Wistar大鼠单侧肾切除。肾病大鼠未接受治疗或接受螺内酯（400 mg/kg体重/天）、西拉普利（1 mg/kg体重/天）或两者治疗10周。肾炎诱导后1周，未处理大鼠的蛋白尿增加，并在整个实验过程中保持不变。与未治疗动物（212.9 +/- 49.2 mg/天）相比，在抗体注射后第70天，螺内酯治疗组（62.0 +/- 4.0 mg/天，p = 0.0046）和西拉普利治疗组（71.8 +/- 26.0 mg/天，p = 0.0048）的蛋白尿显著减少。在螺内酯+西拉普利治疗组中检测到蛋白尿进一步减少（42.4 +/- 4.5 mg/天，p = 0.0019，与未治疗组相比）和肾皮质间质纤维化变化较少（纤维化评分：142.0 +/- 18.4与未治疗组80.3 +/- 18.5，p = 0.0123）。三个治疗组之间的血压没有差异。总之，螺内酯改善蛋白尿的程度与西拉普利相同，同时使用螺内酯和ACE抑制剂可进一步抑制肾脏疾病的进展。这些数据表明，螺内酯和ACE抑制剂的联合治疗对免疫引发的进行性肾脏疾病具有有益作用。
Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticoid receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (1 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9 +/- 49.2 mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0 +/- 4.0 mg/day, p = 0.0046) and the cilazapril-treated group (71.8 +/- 26.0 mg/day, p = 0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4 +/- 4.5 mg/day, p = 0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0 +/- 18.4 vs. 80.3 +/- 18.5 in the untreated group, p = 0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.