Renal Antifibrotic Effect of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline in Diabetic Rats

被引：33

作者：

Castoldi, G. ^{[1
]}

di Gioia, C. R. T. ^{[2
]}

Bombardi, C. ^{[1
]}

Preziuso, C. ^{[2
]}

Leopizzi, M. ^{[2
]}

Maestroni, S. ^{[3
]}

Corradi, B. ^{[1
]}

Zerbini, G. ^{[3
]}

Stella, A. ^{[1
]}

机构：

[1] Univ Milano Bicocca, Dipartimento Sci Salute, Az Osped San Gerardo, IT-20900 Monza, Italy

[2] Univ Roma La Sapienza, Ist Anat Patol, Dipartimento Sci Radiol Oncol & Anatomopatol, Rome, Italy

[3] Ist Sci San Raffaele, Unita Complicanze Diabet, Div Sci Metabol & Cardiovasc, Milan, Italy

来源：

AMERICAN JOURNAL OF NEPHROLOGY | 2013年 / 37卷 / 01期

关键词：

Diabetic nephropathy; Experimental models; Fibrosis; Rats; N-acetyl-seryl-aspartyl-lysyl-proline; Angiotensin-converting enzyme inhibitors; CONVERTING ENZYME-INHIBITION; AC-SDKP; FIBROSIS; INFLAMMATION; DYSFUNCTION; REGULATOR; MECHANISM; PLASMA; GROWTH;

D O I：

10.1159/000346116

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background and Aim: Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl- proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis. Method: Diabetes was induced in 28 Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin. Control rats (n = 10) received only buffer solution. An ACE inhibitor (ramipril, 3 mg/kg/day) was administered to 11 diabetic rats. After 2 months, Ac-SDKP (1 mg/kg/day) was administered by osmotic minipumps for 8 weeks to 7 diabetic rats and to 6 diabetic rats treated with ramipril. Osmotic minipumps delivered saline solution in the corresponding sham-treated rats (diabetic rats, n = 10, and ramipril-treated diabetic rats, n = 5). Results: Diabetic rats showed a significant increase in blood glucose level, urinary albumin excretion and renal fibrosis, and a reduction of glomerular nephrin expression with respect to control rats. Ac-SDKP administration significantly reduced renal fibrosis in diabetic rats, without significantly reducing urinary albumin excretion. Ramipril treatment caused a significant decrease in albuminuria and renal fibrosis and restored glomerular nephrin expression. Administration of Ac-SDKP, in addition to ramipril, further reduced renal fibrosis with respect to ramipril alone, while it did not improve the antiproteinuric effect of ramipril. Conclusion: AcSDKP administration reduces renal fibrosis in diabetic nephropathy. Addition of Ac-SDKP to ACE inhibition therapy improves the reduction of renal fibrosis with respect to ACE inhibition alone, suggesting a beneficial effect of this pharmacological association in diabetic nephropathy. Copyright (C) 2013 S. Karger AG, Basel

引用

页码：65 / 73

页数：9

共 25 条

[1] Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline [J].