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硫辛酸对糖尿病大鼠视网膜血管生成因子表达的影响。

Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina.

机构信息

Department of Ophthalmology, College of Medicine, Inje University, Busan Paik Hospital, Busan, Korea.

出版信息

Clin Exp Ophthalmol. 2012 Jan-Feb;40(1):e47-57. doi: 10.1111/j.1442-9071.2011.02695.x. Epub 2011 Nov 4.

Abstract

BACKGROUND

This study evaluated the effect of a lipoic acid on reactive oxygen species formation and the simultaneous changes of several angiogenic factors in an experimental diabetic rat retina.

METHODS

Diabetes was induced chemically by intraperitoneal injection of streptozotocin in 30 Sprague-Dawley rats. After inducing diabetes, lipoic acid (10 mg/kg) was administered to 10 rats orally. The rats were divided into normal, diabetes mellitus, and lipoic acid-treated groups (each group n = 10). The eyeballs were harvested 8 weeks after inducing diabetes. The expression of vascular endothelial growth factor, erythropoietin, angiopoietin 1 and 2 and NADPH oxidase was examined in the rat retina using reverse transcription-polymerase chain reaction and Western blot. Superoxide formation was examined using dihydroethidium stain.

RESULTS

Dihydroethidium analyses showed increased superoxide formation in the retina of the diabetic group. The superoxide formation was suppressed with lipoic acid treatment. Western blot analysis showed that NADPH oxidase was decreased in the diabetic group and returned to normal level in the lipoic acid-treated group. Treatment with lipoic acid blocked hyperglycaemia induced increases of vascular endothelial growth factor, angiopoietin 2 and erythropoietin shown by reverse transcription-polymerase chain reaction and Western blot analysis.

CONCLUSIONS

Lipoic acid treatment suppressed expression of vascular endothelial growth factor, angiopoietin 2 and erythropoietin via blockade of superoxide formation. Antioxidant treatment is suspected to have an antiangiogenic effect.

摘要

背景

本研究评估了硫辛酸对实验性糖尿病大鼠视网膜中活性氧形成的影响,以及几种血管生成因子的同时变化。

方法

30 只 Sprague-Dawley 大鼠通过腹腔注射链脲佐菌素化学诱导糖尿病。诱导糖尿病后,10 只大鼠口服给予硫辛酸(10mg/kg)。将大鼠分为正常组、糖尿病组和硫辛酸治疗组(每组 n = 10)。诱导糖尿病 8 周后采集眼球。采用逆转录-聚合酶链反应和 Western blot 检测大鼠视网膜中血管内皮生长因子、促红细胞生成素、血管生成素 1 和 2 以及 NADPH 氧化酶的表达。使用二氢乙啶染色检测超氧化物的形成。

结果

二氢乙啶分析显示糖尿病组视网膜中超氧化物形成增加。硫辛酸治疗抑制了超氧化物的形成。Western blot 分析显示,糖尿病组 NADPH 氧化酶减少,而硫辛酸治疗组恢复正常水平。硫辛酸治疗通过阻断超氧化物形成,阻止了血管内皮生长因子、血管生成素 2 和促红细胞生成素的高血糖诱导增加,逆转录-聚合酶链反应和 Western blot 分析均显示这一点。

结论

硫辛酸治疗通过抑制血管内皮生长因子、血管生成素 2 和促红细胞生成素的表达来抑制超氧化物的形成。抗氧化治疗可能具有抗血管生成作用。

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