Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration
Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration
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DOI：
10.1007/s00441-020-03267-w
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发表时间：
2020-08-12
影响因子：
3.6
通讯作者：
Kong, Li
中科院分区：
文献类型：
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作者：
Lv, Jinjuan;Bao, Shuyin;Kong, Li
糖尿病视网膜病变（DR）是由高血糖引起的一种严重的神经退行性疾病。萝卜硫素（sulforaphan， SF）广泛存在于十字花科植物中，对糖尿病视网膜神经退行性变具有保护作用，但其机制尚不清楚。在本研究中，我们探讨了SF对糖尿病光感受器变性的保护机制。在体内，采用链脲佐菌素（STZ）注射建立小鼠糖尿病模型，分别给药/不给药。视网膜电图（ERG）和H&E染色评价视网膜功能和形态。在体外，661w细胞分别用含/不含SF的AGEs处理。采用CCK-8法和流式细胞术分析细胞活力和凋亡情况。western blot和qRT-PCR检测蛋白和基因的表达情况。糖尿病小鼠的脑电波振幅降低，脑电波形态发生改变，SF治疗可延缓这些变化。661w细胞经AGEs处理后，凋亡细胞比例增加，细胞活力降低。此外，grp78、TxnipandTNF α的表达增加，然而，SF通过AMPK通路激活逆转了这种增加的表达。综上所述，SF可延缓糖尿病光感受器变性，其潜在机制可能与通过激活AMPK通路抑制内质网应激、炎症和txnipp表达有关。
Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of thea-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression ofGRP78,TxnipandTNF alpha was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation andTxnipexpression through the activation of the AMPK pathway.