Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function.

Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function.
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脱氢表雄酮治疗糖尿病大鼠对血管和神经功能的影响。

DOI:
10.1152/ajpendo.00173.2002
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发表时间:
2002
期刊:
American journal of physiology. Endocrinology and metabolism
影响因子:
--
通讯作者:
Dillon,JosephS
Dillon,JosephS
中科院分区:
--
文献类型:
--
作者:
Yorek,MarkA;Coppey,LawrenceJ;Gellett,JillS;Davidson,EricP;Bing,Xinyu;Lund,DonaldD;Dillon,JosephS

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脱氢表雄酮(DHEA)的营养补充可能是治疗糖尿病引起的血管和神经功能障碍的候选药物。脱氢表雄酮是一种自然产生的肾上腺雄激素,具有抗氧化特性,据报道在糖尿病患者中会减少。使用预防方案,我们发现饮食补充0.1%、0.25%或0.5%DHEA的链脲佐菌素诱导的糖尿病大鼠的运动神经传导速度和神经内膜血流障碍的发展具有浓度依赖性的预防作用,而糖尿病大鼠的运动神经传导速度和神经内血流障碍则有所降低。0.25%的DHEA显著阻止了糖尿病引起的血清硫代巴比妥酸反应物质和坐骨神经共轭双烯水平的增加。这种治疗还减少了坐骨神经外膜小动脉产生的超氧化物。DHEA(0.25%)可显著改善乙酰胆碱介导的糖尿病大鼠神经外膜血管的舒张性。DHEA还能提高坐骨神经Na+-K+-ATPase活性和肌醇含量,但山梨醇和果糖含量仍较高。这些研究表明,脱氢表雄酮通过预防氧化应激,可能改善坐骨神经Na+-K+-ATPase活性,可能改善糖尿病患者的血管和神经功能障碍。
Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes-induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin-induced diabetic rats with 0.1, 0.25, or 0.5% DHEA caused a concentration-dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment, which are decreased in diabetes. At 0.25%, DHEA significantly prevented the diabetes-induced increase in serum thiobarbituric acid-reactive substances and sciatic nerve conjugated diene levels. This treatment also reduced the production of superoxide by epineurial arterioles of the sciatic nerve. DHEA treatment (0.25%) significantly improved vascular relaxation mediated by acetylcholine in epineurial vessels of diabetic rats. Sciatic nerve Na+-K+-ATPase activity and myoinositol content was also improved by DHEA treatment, whereas sorbitol and fructose content remained elevated. These studies suggest that DHEA, by preventing oxidative stress and perhaps improving sciatic nerve Na+-K+-ATPase activity, may improve vascular and neural dysfunction in diabetes.