维生素E和C补充剂联合口服抗糖尿病疗法对新生期注射链脲佐菌素的糖尿病大鼠内皮功能障碍的影响。

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat.

作者信息

Alper Gülinnaz, Olukman Murat, Irer Seda, Cağlayan Osman, Duman Erdal, Yilmaz Candeğer, Ulker Sibel

机构信息

Department of Biochemistry, Faculty of Medicine, Ege University, Izmir, Turkey.

出版信息

Diabetes Metab Res Rev. 2006 May-Jun;22(3):190-7. doi: 10.1002/dmrr.586.

DOI:10.1002/dmrr.586

PMID:16216038

Abstract

BACKGROUND

This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type-2 diabetes in rat.

METHODS

Diabetes was induced by streptozotocin injection to neonatal rats which were breastfed for 4 weeks, then fed 6 weeks with normal food or food supplemented with 2% vitamin E and 4% vitamin C. Some diabetic rats were treated with gliclazide for 6 weeks. Endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside (SNP) were recorded in thoracic aortic rings. Plasma insulin, HbA(1c) and antioxidant vitamins (A, C and E); plasma and aortic malondialdehyde (MDA) levels were determined.

RESULTS

Induction of diabetes resulted in decreased body weight and increased blood glucose, plasma insulin and HbA(1c) levels compared to controls. Acetylcholine relaxation was impaired in diabetic aorta, while SNP relaxation remained unchanged. Aortic MDA level was significantly higher, while plasma vitamin levels were lower in diabetic rats. Diminished acetylcholine response, enhanced aortic MDA level and decreased plasma vitamin levels were all restored after gliclazide and/or vitamin therapy. However, vitamin supplementation in control rats significantly impaired acetylcholine relaxations and increased aortic MDA levels.

CONCLUSIONS

Apparently, a selective endothelial dysfunction accompanies the imbalance in oxidant/antioxidant status in the type-2 diabetes model of rat and gliclazide and/or vitamin supplementation improves the impairment in diabetic vasculature. However, vitamin supplementation triggers oxidative stress in normal aortic tissue, thereby, leads to endothelial dysfunction; indicating that nutritional extra-supplementation of antioxidant vitamins isn't advisable for normal subjects, although it's beneficial in disease status.

摘要

背景

本研究在大鼠2型糖尿病模型中，探究维生素补充剂对口服抗糖尿病疗法逆转内皮功能障碍疗效的作用。

方法

通过向新生大鼠注射链脲佐菌素诱导糖尿病，这些大鼠母乳喂养4周，然后用正常食物或添加2%维生素E和4%维生素C的食物喂养6周。一些糖尿病大鼠用格列齐特治疗6周。记录胸主动脉环对乙酰胆碱和硝普钠（SNP）的内皮依赖性和非内皮依赖性舒张反应。测定血浆胰岛素、糖化血红蛋白（HbA1c）和抗氧化维生素（A、C和E）；血浆和主动脉丙二醛（MDA）水平。

结果

与对照组相比，糖尿病诱导导致体重减轻，血糖、血浆胰岛素和HbA1c水平升高。糖尿病大鼠主动脉对乙酰胆碱的舒张反应受损，而对SNP的舒张反应保持不变。糖尿病大鼠主动脉MDA水平显著升高，而血浆维生素水平较低。格列齐特和/或维生素治疗后，乙酰胆碱反应减弱、主动脉MDA水平升高和血浆维生素水平降低均得到恢复。然而，对照组大鼠补充维生素显著损害了乙酰胆碱舒张反应并增加了主动脉MDA水平。