Effect of long-term administration of α-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats
Effect of long-term administration of α-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats
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DOI：
10.2337/diabetes.53.12.3233
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Odenbach, S
中科院分区：
文献类型：
--
作者：
Kowluru, RA;Odenbach, S
糖尿病视网膜中的氧化应激增加，并且它被认为在视网膜病变的发展中起重要作用。α-硫辛酸是一种硫醇抗氧化剂，已显示对多发性神经病和各种组织（包括神经、肾和视网膜）中的氧化应激参数具有有益作用。本研究的目的是检测α-硫辛酸对糖尿病视网膜毛细血管细胞凋亡和病理发展的影响。视网膜来自链脲佐菌素诱导的糖尿病大鼠，其接受补充有或没有α-硫辛酸（400 mg/kg）的饮食，持续11个月的糖尿病。在胰蛋白酶消化的视网膜微血管中研究毛细血管细胞凋亡（通过末端转移酶介导的dUTP缺口末端标记）和无细胞毛细血管的形成。用酶联免疫吸附试验测定给予异辛酸对视网膜8-羟基-2 '-脱氧鸟苷（8-OHdG）和硝基酪氨酸水平的影响。尽管两个糖尿病组（有和没有α-硫辛酸）中高血糖症的严重程度相似，但在糖尿病的整个持续时间内施用α-硫辛酸抑制了视网膜中毛细血管细胞凋亡和无细胞毛细血管的数量。视网膜8-OHdG和硝基酪氨酸水平分别增加了两倍以上和70%，在糖尿病，和α-硫辛酸管理抑制这些增加。我们的研究结果表明，长期给予α-硫辛酸通过抑制视网膜中氧化修饰的DNA和硝基酪氨酸的积累对糖尿病视网膜病变的发展具有有益作用。α-硫辛酸补充剂代表了一种可实现的辅助治疗，以帮助预防糖尿病患者的视力丧失。
Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. alpha-Lipoic acid, a thiol antioxidant, has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerve, kidney, and retina. The purpose of this study was to examine the effect of alpha-lipoic acid on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without alpha-lipoic acid (400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of et-lipoic acid administration on retinal 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked inmunosorbent assay. alpha-Lipoic acid administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the two diabetic groups (with and without alpha-lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over twofold and 70%, respectively, in diabetes, and alpha-lipoic acid administration inhibited these increases. Our results demonstrate that the long-term administration of a-lipoic acid has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. alpha-Lipoic acid supplementation represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.