Ozdemir G, Ergün Y, Bakariş S, Kılınç M, Durdu H, Ganiyusufoğlu E
Department of Ophthalmology, Faculty of Medicine, Kahramanmaraş Sütçüimam University, Kahramanmaraş, Turkey.
Department of Pharmacology, Faculty of Medicine, Kahramanmaraş Sütçüimam University, Kahramanmaraş, Turkey.
Eye (Lond). 2014 Aug;28(8):1020-7. doi: 10.1038/eye.2014.127. Epub 2014 Jun 13.
To evaluate the role of melatonin, an antioxidant agent, in diabetic oxidative stress and vascular damage.
Diabetes was induced in 21 male Wistar rats by intraperitoneal (IP) administration of streptozotocin and then the rats were equally and randomly allocated to diabetic, melatonin, and vehicle groups. Seven healthy normal rats with similar features comprised the control group as the fourth group. All animals were followed for 12 weeks. The melatonin group received IP melatonin daily and the vehicle group received 2.5% ethanol IP at the last month. At the end of 12 weeks, the rats were killed and retinas were harvested. The retinas were investigated for the existence of hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor A (VEGF-A), and pigment epithelium-derived factor (PEDF) by ELISA. Retinal oxidative stress is quantitated by measuring nitrotyrosine and malondialdehyde levels. Retinal immunohistochemistry with antibody against CD31 antigen was carried out on retinal cross-sections. For statistics, ANOVA test was used for multiple comparisons.
Hyperglycemia increased retinal oxidation as measured through levels of nitrotyrosine and malondialdehyde. Diabetic retinas are also associated with abnormal vascular changes such as dilatation and deformation. HIF-1α, VEGF-A, and PEDF were all increased because of diabetic injury. Melatonin showed a potential beneficial effect on retinopathy in diabetic rats. It decreased retinal nitrotyrosine and malondialdehyde levels, showing an antioxidative support. The vasculomodulator cytokines are decreased accordingly by melatonin therapy. Melatonin normalized retinal vascular changes as well.
Melatonin may show some advantage on diabetic vascular changes through decreasing oxidative stress and vessel-related cytokines.
评估抗氧化剂褪黑素在糖尿病氧化应激和血管损伤中的作用。
通过腹腔注射链脲佐菌素诱导21只雄性Wistar大鼠患糖尿病，然后将大鼠平均随机分为糖尿病组、褪黑素组和溶剂对照组。选取7只特征相似的健康正常大鼠作为第四组即对照组。所有动物均观察12周。褪黑素组每天腹腔注射褪黑素，溶剂对照组在最后一个月腹腔注射2.5%乙醇。12周结束时，处死大鼠并摘取视网膜。通过酶联免疫吸附测定法检测视网膜中缺氧诱导因子1-α（HIF-1α）、血管内皮生长因子A（VEGF-A）和色素上皮衍生因子（PEDF）的存在情况。通过测量硝基酪氨酸和丙二醛水平对视网膜氧化应激进行定量分析。对视网膜横断面进行抗CD31抗原抗体的视网膜免疫组织化学检测。统计学分析采用方差分析进行多重比较。
通过硝基酪氨酸和丙二醛水平测量发现，高血糖会增加视网膜氧化。糖尿病视网膜还伴有血管异常变化，如扩张和变形。糖尿病损伤导致HIF-1α、VEGF-A和PEDF均升高。褪黑素对糖尿病大鼠视网膜病变显示出潜在的有益作用。它降低了视网膜硝基酪氨酸和丙二醛水平，显示出抗氧化支持作用。褪黑素治疗相应地降低了血管调节细胞因子水平。褪黑素还使视网膜血管变化恢复正常。
褪黑素可能通过降低氧化应激和血管相关细胞因子，对糖尿病血管变化显示出一定优势。
