Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy.
Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy.
复制标题
褪黑激素对实验性糖尿病视网膜病变视网膜炎症和氧化应激的保护作用。
DOI：
10.1155/2016/3528274
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发表时间：
2016
影响因子：
--
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Jiang T;Chang Q;Cai J;Fan J;Zhang X;Xu G
氧化应激和炎症是导致糖尿病视网膜病变（DR）病因的重要致病因素。褪黑素是一种内源性激素，具有多种生物学效应，包括抗氧化和抗炎功能。本研究的目的是确定褪黑素是否能够改善视网膜损伤，并探索其潜在机制。通过单次腹腔注射链脲佐菌素（STZ，60mg/kg）在Sprague - Dawley大鼠中诱导糖尿病。从诱导糖尿病开始，每天腹腔注射褪黑素（10mg/kg），持续12周，之后处死动物并收集视网膜样本。糖尿病大鼠的视网膜显示谷胱甘肽耗竭以及谷氨酸半胱氨酸连接酶（GCL）下调。褪黑素通过将核因子E2相关因子2（Nrf2）保留在细胞核内并刺激蛋白激酶B（Akt）磷酸化，显著上调GCL。褪黑素通过核因子κB（NF - κB）通路抑制包括白细胞介素1β、肿瘤坏死因子 - α和诱导型一氧化氮合酶（iNOS）在内的促炎细胞因子和蛋白质的产生。在12周时，褪黑素阻止了糖尿病条件下视网膜电图（ERG）a波和b波振幅的显著下降。我们的研究结果表明褪黑素在糖尿病视网膜病变中具有强大的保护作用。除了作为一种直接的抗氧化剂外，褪黑素还可以发挥受体介导的信号传导作用，以减轻视网膜的炎症和氧化应激。
Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.