Ruiz-Ortega M, González S, Serón D, Condom E, Bustos C, Largo R, González E, Ortiz A, Egido J
Renal Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Kidney Int. 1995 Dec;48(6):1778-91. doi: 10.1038/ki.1995.476.
We studied the effect of the angiotensin converting enzyme (ACE) inhibitor, quinapril, on the clinical and morphological lesions of a normotensive model of immune complex nephritis. Untreated rats developed massive nephrotic syndrome, intense cell proliferation and glomerular and tubulointerstitial lesions. In the renal cortex of nephritic rats there was a significant increase in gene expression of TGF-beta 1, fibronectin and collagens, and ACE activity. Systolic blood pressure remained normal with progression of the disease. Administration of quinapril for three weeks to animals with glomerular lesions (proteinuria 20 to 50 mg/day) avoided the development of intense proteinuria (79 +/- 28 vs. 589 +/- 73 mg/day, P < 0.001) and decreased cell proliferation, glomerulosclerosis, tubulointerstitial lesions, and inflammatory infiltrates. Cortical gene expression of TGF-beta 1 and matrix proteins was also diminished. ACE activity was inhibited by 68% in renal cortex. These results show that quinapril administration to normotensive rats with immune complex nephritis decreases proteinuria and glomerular and tubulointerstitial lesions, probably modulating the local angiotensin II generation and its effects on cell growth, TGF beta and matrix protein synthesis.
我们研究了血管紧张素转换酶（ACE）抑制剂喹那普利对免疫复合物性肾炎正常血压模型的临床和形态学损伤的影响。未经治疗的大鼠出现大量肾病综合征、强烈的细胞增殖以及肾小球和肾小管间质损伤。在肾炎大鼠的肾皮质中，转化生长因子β1（TGF-β1）、纤连蛋白和胶原蛋白的基因表达以及ACE活性显著增加。随着疾病进展，收缩压保持正常。对有肾小球损伤（蛋白尿20至50毫克/天）的动物给予喹那普利三周，可避免严重蛋白尿的发生（79±28对589±73毫克/天，P<0.001），并减少细胞增殖、肾小球硬化、肾小管间质损伤和炎性浸润。肾皮质中TGF-β1和基质蛋白的基因表达也有所减少。肾皮质中的ACE活性被抑制了68%。这些结果表明，对患有免疫复合物性肾炎的正常血压大鼠给予喹那普利可减少蛋白尿以及肾小球和肾小管间质损伤，可能是通过调节局部血管紧张素II的生成及其对细胞生长、TGF-β和基质蛋白合成的影响来实现的。
