Pfister Frederick, Riedl Eva, Wang Qian, vom Hagen Franziska, Deinzer Martina, Harmsen Martin Conrad, Molema Grietje, Yard Benito, Feng Yuxi, Hammes Hans-Peter
5th Medical Department, University Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Cell Physiol Biochem. 2011;28(1):125-36. doi: 10.1159/000331721. Epub 2011 Aug 16.
BACKGROUNDS/AIMS: Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic retinopathy. In this study, the effect of the antioxidant and antiglycating dipeptide carnosine was studied on the development of experimental diabetic retinopathy.
MATERIALS/METHODS: STZ-induced diabetic Wistar rats were orally treated with carnosine (1g/kg body weight/day). Retinal vascular damage was assessed by quantitative morphometry. Retinal protein extracts were analyzed for markers of oxidative stress, AGE-formation, activation of the hexosamine pathway and changes in the expression of Ang-2, VEGF and heat shock proteins Hsp27 and HO-1. Glial cell activation was analyzed using Western blot analysis and immunofluorescence of GFAP expression and retinal neuronal damage was histologically examined.
Oral carnosine treatment prevented retinal vascular damage after 6 months of experimental hyperglycemia. The protection was not caused by ROS- or AGE-inhibition, but associated with a significant induction of Hsp27 in activated glial cells and normalization of increased Ang-2 levels in diabetic retinas. A significant reduction of photoreceptors in retinas of carnosine treated animals was noted.
Oral carnosine treatment protects retinal capillary cells in experimental diabetic retinopathy, independent of its biochemical function. The vasoprotective effect of carnosine might be mediated by the induction of protective Hsp27 in activated glial cells and normalization of hyperglycemia-induced Ang-2.
背景/目的：周细胞丢失、血管消退和神经胶质激活是早期糖尿病视网膜病变的特征性变化。在本研究中，对抗氧化和抗糖化二肽肌肽对实验性糖尿病视网膜病变发展的影响进行了研究。
材料/方法：用链脲佐菌素诱导的糖尿病Wistar大鼠口服肌肽（1克/千克体重/天）。通过定量形态学评估视网膜血管损伤。分析视网膜蛋白提取物中的氧化应激标志物、晚期糖基化终末产物形成、己糖胺途径激活以及血管生成素-2（Ang-2）、血管内皮生长因子（VEGF）和热休克蛋白Hsp27及血红素氧合酶-1（HO-1）表达的变化。使用蛋白质免疫印迹分析和胶质纤维酸性蛋白（GFAP）表达的免疫荧光分析胶质细胞激活情况，并通过组织学检查视网膜神经元损伤。
口服肌肽治疗可预防实验性高血糖6个月后的视网膜血管损伤。这种保护作用不是由抑制活性氧或晚期糖基化终末产物引起的，而是与激活的胶质细胞中Hsp27的显著诱导以及糖尿病视网膜中升高的Ang-2水平恢复正常有关。注意到肌肽治疗动物的视网膜中光感受器显著减少。
口服肌肽治疗可保护实验性糖尿病视网膜病变中的视网膜毛细血管细胞，与其生化功能无关。肌肽的血管保护作用可能是通过在激活的胶质细胞中诱导保护性Hsp27以及使高血糖诱导的Ang-2恢复正常来介导的。
