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体内给予替米沙坦对链脲佐菌素诱导的糖尿病大鼠的肾脏保护作用。

Renal protection of in vivo administration of tempol in streptozotocin-induced diabetic rats.

机构信息

Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.

出版信息

J Pharmacol Sci. 2012;119(2):167-76. doi: 10.1254/jphs.12002fp. Epub 2012 May 22.

Abstract

The present study was carried out to investigate the protective effects of tempol on renal function and the underlying mechanism in streptozotocin-induced diabetic rats. The diabetic rats were randomly divided into the model group (without tempol) and tempol group (1 mM tempol in drinking water for 6 weeks). Nondiabetic rats were served as the Control group. The mRNA expression of canonical transient receptor potential 6 (TRPC6), transforming growth factor (TGF)-β1, and type IV collagen (Col IV) were examined. The malondialdehyde (MDA) level, activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in renal tissues were measured to assess redox status in kidneys. We found that tempol significantly reduced 24-h urine output and urine albuminuria excretion in the diabetic rats. Compared with the model group, the concentration of MDA was significantly lower in the tempol group. In addition, diabetes decreased activities of SOD and GSH-Px and these responses were prevented by tempol treatment. Moreover, in diabetic rats, the mRNA expression levels of TGF-β1 and Col IV were upregulated. TRPC6 mRNA expression level was down-regulated in diabetic kidneys. However, all of these diabetic effects were significantly suppressed by tempol treatment. These results suggest that chronic treatment of diabetic rats with tempol can protect kidneys, possibly by reducing expression of TGF-β1, Col IV, and upregulating TRPC6 expression level.

摘要

本研究旨在探讨替米沙坦对链脲佐菌素诱导的糖尿病大鼠肾功能的保护作用及其机制。将糖尿病大鼠随机分为模型组(无替米沙坦)和替米沙坦组(饮用水中添加 1mM 替米沙坦,持续 6 周)。非糖尿病大鼠作为对照组。检测经典瞬时受体电位 6(TRPC6)、转化生长因子(TGF)-β1 和 IV 型胶原(Col IV)的 mRNA 表达。测量肾脏组织中丙二醛(MDA)水平、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性,以评估肾脏的氧化还原状态。结果发现,替米沙坦可显著减少糖尿病大鼠的 24 小时尿量和尿白蛋白排泄量。与模型组相比,替米沙坦组 MDA 浓度显著降低。此外,糖尿病降低了 SOD 和 GSH-Px 的活性,而替米沙坦治疗可预防这些反应。此外,在糖尿病大鼠中,TGF-β1 和 Col IV 的 mRNA 表达水平上调。糖尿病肾脏中 TRPC6 mRNA 表达水平下调。然而,替米沙坦治疗显著抑制了所有这些糖尿病效应。这些结果表明,替米沙坦对糖尿病大鼠的慢性治疗可保护肾脏,可能是通过降低 TGF-β1、Col IV 的表达和上调 TRPC6 的表达水平。

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