Renal Antifibrotic Effect of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline in Diabetic Rats
Renal Antifibrotic Effect of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline in Diabetic Rats
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DOI：
10.1159/000346116
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发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
Stella, A.
中科院分区：
文献类型：
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作者：
Castoldi, G.;di Gioia, C. R. T.;Stella, A.
背景与目的：糖尿病肾病是终末期肾病的主要原因。 N-乙酰基-丝氨酰-赖氨酰-脯氨酸 (Ac-SDKP) 是一种被血管紧张素转换酶 (ACE) 水解的生理四肽，在高血压、心力衰竭和肾脏疾病的实验模型中对心血管系统和肾脏具有抗纤维化作用。该研究的目的是评估 Ac-SDKP 在糖尿病肾病中的作用，以及与单独使用 ACE 抑制剂相比，Ac-SDKP 对肾纤维化发展的潜在附加作用。方法：通过单次腹腔注射链脲佐菌素诱导 28 只 Sprague-Dawley 大鼠患糖尿病。对照大鼠 (n = 10) 仅接受缓冲溶液。对 11 只糖尿病大鼠施用 ACE 抑制剂（雷米普利，3 mg/kg/天）。 2个月后，通过微型渗透泵向7只糖尿病大鼠和6只用雷米普利治疗的糖尿病大鼠施用Ac-SDKP（1毫克/千克/天），持续8周。渗透微型泵向相应的假治疗大鼠（糖尿病大鼠，n = 10，雷米普利治疗的糖尿病大鼠，n = 5）输送盐溶液。结果：与对照大鼠相比，糖尿病大鼠的血糖水平、尿白蛋白排泄和肾纤维化显着增加，并且肾小球去氧肾上腺素表达减少。 Ac-SDKP 给药可显着减少糖尿病大鼠的肾纤维化，但不会显着减少尿白蛋白排泄。雷米普利治疗导致白蛋白尿和肾纤维化显着减少，并恢复肾小球去氧肾上腺素表达。与单独使用雷米普利相比，除了雷米普利外，Ac-SDKP 的给药进一步减少了肾纤维化，但没有提高雷米普利的抗蛋白尿作用。结论：AcSDKP 给药可减少糖尿病肾病的肾纤维化。与单独使用 ACE 抑制相比，在 ACE 抑制疗法中添加 Ac-SDKP 可改善肾纤维化的减少，表明这种药理学联合对糖尿病肾病具有有益作用。版权所有 (C) 2013 S. Karger AG，巴塞尔
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