Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor β1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat
Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor β1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat
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肾素-血管紧张素系统阻断可防止链脲佐菌素糖尿病大鼠血浆转化生长因子β1的增加，并减少蛋白尿和肾脏肥大
DOI：
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
D. J. van Dijk
中科院分区：
文献类型：
--
作者：
A. Erman;S. Veksler;U. Gafter;G. Boner;C. Wittenberg;D. J. van Dijk
血管紧张素转换酶（ACE）抑制剂和血管紧张素受体阻滞剂（ARB）的联合治疗用于改善糖尿病患者单药治疗的肾脏结局。此外，干扰肾素-血管紧张素系统（RAS）可减少糖尿病肾病中转化生长因子β1（TGF-β1）的表达和排泄。本研究旨在观察血管紧张素转换酶抑制剂（ACE-I）、血管紧张素转换酶抑制剂（ARB）单药或联合用药阻断RAS对糖尿病大鼠蛋白尿、肾脏肥大和血浆转化生长因子β1（TGF-β1）的影响。材料与方法41只雄性Wistar大鼠随机分为5组：1组为正常对照组，2组为糖尿病组（链脲佐菌素[STZ] 55 mg/kg），3组为糖尿病组（依那普利20 mg/kg/d），4组为糖尿病组（氯沙坦80 mg/kg/d），5组为糖尿病组（氯沙坦+依那普利）。这项研究持续了60天。结果糖尿病大鼠尿蛋白排泄量、肾脏重量、血清ACE活性和血浆TGF-β1水平均显著高于对照组。给予氯沙坦、依那普利或两者联合治疗60天可防止这些变化。此外，30天的联合治疗使尿蛋白排泄正常化，而单药治疗则没有。氯沙坦在体内外均能抑制血清ACE活性。血浆TGF-β1水平与血糖水平（r=0.4059）和尿蛋白排泄量（r=0.3558）呈正相关。结论氯沙坦和依那普利联合治疗在早期抗蛋白尿反应方面比单药治疗更有效。氯沙坦长期治疗与联合治疗一样有效，可能是由于对RAS的双重抑制作用。抗蛋白尿作用可能部分与降低TGF-β1有关。
Introduction Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor β1 (TGF-β1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-β1 in diabetic rats. Materials and methods Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. Results Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-β1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-β1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). Conclusions Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-β1.
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血管紧张素II诱导的肾小管肥大。
DOI：
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发表时间：
1997
期刊：
Seminars in nephrology.
影响因子：
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作者：
Wolf,G;Ziyadeh,FN
通讯作者：
Ziyadeh,FN
影响因子：
8.3
作者：
Navar, LG;Harrison-Bernard, LM;Kobori, H
通讯作者：
Kobori, H
影响因子：
--
作者：
ANDERSON, S;JUNG, FF;INGELFINGER, JR
通讯作者：
INGELFINGER, JR
缓激肽抑制 EGF 和 PDGF 诱导的人成纤维细胞 DNA 合成。
DOI：
10.1152/ajpcell.1993.265.2.c477
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
McAllister,BS;Leeb-Lundberg,F;Olson,MS
通讯作者：
Olson,MS
血管紧张素 II 在肾纤维化中的作用：治疗目标应该是 TGF-β 而不是血压？
DOI：
--
发表时间：
1997
期刊：
Seminars in nephrology.
影响因子：
--
作者：
Noble,NA;Border,WA
通讯作者：
Border,WA