Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice.
Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice.
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DOI：
10.18632/oncotarget.18134
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Kong L
中科院分区：
文献类型：
--
作者：
Ren X;Li C;Liu J;Zhang C;Fu Y;Wang N;Ma H;Lu H;Kong H;Kong L
糖尿病是一种慢性代谢综合征，其导致碳水化合物、脂质和蛋白质代谢的改变。长期伴随糖尿病，会增加糖尿病视网膜病变（DR）的风险和长期发病率及死亡率。此外，新出现的证据表明，神经元损伤发生早于DR患者的微血管并发症，但其潜在机制尚不清楚。我们研究了糖尿病诱导的视网膜神经病变，并阐明了关键的分子事件，以确定新的治疗目标的临床治疗和预防DR。在体内研究中，高脂肪饮食和链脲佐菌素（STZ）注射用于生成糖尿病模型。苏木精-伊红染色用于形态学观察和外核层厚度的测量。视网膜电图（ERG）用于评估视网膜功能。对于体外研究，将Neuro 2a细胞在正常（5.5 mM）和高葡萄糖（30 mM）条件下孵育。进行流式细胞术测定以分析细胞凋亡。此外，进行实时PCR和蛋白质印迹分析以确定体外和体内的基因和蛋白质表达。总之，结果表明，视网膜神经病变发生在糖尿病引起的内皮损伤之前，硫氧还蛋白（Trx）在此过程中起着关键作用。这一潜在机制可能与Trx/ASK 1/p-p38/Trx相互作用蛋白通路的激活有关。
Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR. For in vivo studies, a high-fat diet and streptozotocin (STZ) injection were used to generate the diabetes model. Hematoxylin-eosin staining was used for morphological observations and measurements of the outer nuclear layer thickness. Electroretinography (ERG) was used to assess retinal function. For in vitro studies, Neuro2a cells were incubated in normal (5.5 mM) and high-glucose (30 mM) conditions. Flow cytometry assays were performed to analyze apoptosis. Additionally, real-time PCR and Western blotting analyses were carried out to determine gene and protein expression in vitro and in vivo. Taken together, the results indicated that retinal neuropathy occurred prior to endothelial damage induced by diabetes, and thioredoxin (Trx) plays a key role in this process. This underlying mechanism may be related to activation of the Trx/ASK1/p-p38/Trx-interacting protein pathway.
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