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司托巴定和维生素E对糖尿病诱导的视网膜异常的影响:氧化应激的作用

Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities: involvement of oxidative stress.

作者信息

Yülek Fatma, Or Meral, Ozoğul Candan, Isik Asli Ceylan, Ari Nuray, Stefek Milan, Bauer Victor, Karasu Cimen

机构信息

Department of Ophthalmalogy, Gazi University, Besevler, Ankara, Turkey.

出版信息

Arch Med Res. 2007 Jul;38(5):503-11. doi: 10.1016/j.arcmed.2007.02.006.

Abstract

BACKGROUND

Because hyperglycemia-induced oxidative stress may be a cause of retinopathy, this study examined the hypothesis that administration of exogenous antioxidants, stobadine (ST) and vitamin E (vitE), can restore retinal abnormalities in experimental diabetes.

METHODS

Normal and streptozotocin (STZ)-induced male Wistar rats received daily intraoral doses of ST (24.7 mg/kg) and vitE (alpha-dl-tocopherol acetate, 400-500 IU/kg) individually or in combinations for 8 months. The biochemical parameters including aldose reductase enzyme (AR) activity and lipid peroxidation (MDA), and histopathological changes such as retinal capillary basement membrane thickness (RCBMT) and vascular endothelial growth factor (VEGF) expression were evaluated.

RESULTS

A 37.99% increase in RCBMT was observed in rats after 8 months diabetes duration. The increase in RCBMT was 12.34% in diabetic rats treated with ST and 23.07% in diabetic rats treated with vitE. In diabetic rats treated with antioxidant combination, just a 4.38% increase was observed in RCBMT. The excess VEGF immunoreactivity and increased MDA and AR activity determined in diabetic retina were significantly attenuated by individual antioxidant treatments. Although both antioxidants decreased blood glucose, HbA1c, fructosamine and triglyceride levels in diabetic rats, poor glycemic control was maintained in all experimental groups during the treatment period. However, the antioxidant combination led to almost complete amelioration in retinal MDA and RCBMT in diabetic rats.

CONCLUSIONS

The ability of antioxidant combination to arrest retinal abnormalities and lipid peroxidation even in the presence of poor glycemic control might advocate the key role of direct oxidative damage and the protective action of antioxidants in retinal alterations associated with diabetic retinopathy.

摘要

背景

由于高血糖诱导的氧化应激可能是视网膜病变的一个原因,本研究检验了以下假设:给予外源性抗氧化剂司托巴定(ST)和维生素E(vitE)可以恢复实验性糖尿病中的视网膜异常。

方法

正常和链脲佐菌素(STZ)诱导的雄性Wistar大鼠每天经口分别或联合给予ST(24.7毫克/千克)和vitE(α-生育酚醋酸酯,400 - 500国际单位/千克),持续8个月。评估了包括醛糖还原酶(AR)活性和脂质过氧化(MDA)在内的生化参数,以及视网膜毛细血管基底膜厚度(RCBMT)和血管内皮生长因子(VEGF)表达等组织病理学变化。

结果

糖尿病病程8个月后,大鼠的RCBMT增加了37.99%。用ST治疗的糖尿病大鼠中RCBMT增加了12.34%,用vitE治疗的糖尿病大鼠中增加了23.07%。在用抗氧化剂组合治疗的糖尿病大鼠中,仅观察到RCBMT增加了4.38%。糖尿病视网膜中过量的VEGF免疫反应性以及增加的MDA和AR活性通过单独的抗氧化剂治疗得到了显著减弱。尽管两种抗氧化剂都降低了糖尿病大鼠的血糖、糖化血红蛋白、果糖胺和甘油三酯水平,但在治疗期间所有实验组的血糖控制都较差。然而,抗氧化剂组合使糖尿病大鼠视网膜中的MDA和RCBMT几乎完全改善。

结论

即使在血糖控制不佳的情况下,抗氧化剂组合阻止视网膜异常和脂质过氧化的能力可能支持直接氧化损伤的关键作用以及抗氧化剂在与糖尿病视网膜病变相关的视网膜改变中的保护作用。

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