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去氢表雄酮(DHEA)对糖尿病大鼠肾功能和代谢的影响。

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

机构信息

Laboratório de Metabolismo e Endocrinologia Comparada, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Sarmento Leite, 500, Porto Alegre, Rio Grande do Sul CEP 90050-170, Brazil.

出版信息

Steroids. 2011 May;76(6):564-70. doi: 10.1016/j.steroids.2011.02.006. Epub 2011 Feb 22.

DOI:10.1016/j.steroids.2011.02.006
PMID:21349280
Abstract

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.

摘要

去氢表雄酮(DHEA)是一种内源性甾体激素,参与人类和啮齿动物的许多生物学作用,但它对肾脏组织的影响尚未完全阐明。本研究旨在评估 DHEA 治疗对糖尿病大鼠的影响,主要涉及肾功能和代谢。糖尿病大鼠通过皮下注射 10mg/kg 剂量的 DHEA 油溶液进行治疗。采用分光光度法定量检测血浆葡萄糖和肌酐,以及尿肌酐。使用放射性葡萄糖定量检测葡萄糖摄取和氧化,采用酶联免疫吸附试验评估尿转化生长因子 β(1)(TGF-β(1)),并测量肾组织中的总谷胱甘肽。糖尿病大鼠血糖水平升高,DHEA 治疗降低了高血糖。DHEA 治疗的糖尿病大鼠血浆肌酐水平升高,而肌酐清除率降低。DHEA 治疗的糖尿病大鼠肾髓质的葡萄糖摄取和氧化降低,而尿 TGF-β(1)和总谷胱甘肽水平升高。DHEA 治疗对肾脏组织没有益处,因为它降低了肾小球滤过率和肾髓质代谢,同时增加了 TGF-β(1)的尿排泄和谷胱甘肽系统的代偿反应,可能是由于这种雄激素或其衍生物的促氧化作用或促纤维化作用的机制所致。总之,本研究报告 DHEA 治疗可能对肾脏组织有害,但这种作用的机制尚未完全阐明。

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