ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway
ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway
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DOI：
10.1016/j.lfs.2018.10.019
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发表时间：
2018-12-15
期刊：
影响因子：
6.1
通讯作者：
Wang, Siwang
中科院分区：
文献类型：
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作者：
He, Mengshan;Long, Pan;Wang, Siwang
目的：乙醛脱氢酶2(ALDH2)对心肌损伤、卒中和神经退行性疾病具有保护作用，但其在糖尿病视网膜病变中的作用和机制尚不清楚。本研究旨在探讨ALDH2对链脲佐菌素(STZ)诱导的老年糖尿病大鼠视网膜损伤的保护作用。主要方法：24只单次腹腔注射STZ诱导的老年糖尿病SD大鼠，随机分为Alda1治疗组和二甲基亚砜(DMSO)组。大鼠于注射STZ前3d和注射后30d分别腹腔注射ALDH2激活剂Alda1(或DMSO)10 mg/kg。分别于造模后1d、7d和30d进行视网膜结构、功能和分子水平的检测。主要结果：光学相干断层扫描(OCT)显示，ALDA1治疗组外核层(ONL)和整个视网膜厚度均大于DMSO组。全场视网膜电图(FfERG)显示Alda1治疗组有较高的波幅(暗适应3.0和OPS)。此外，ALDA1治疗组大鼠视网膜肿瘤坏死因子(TNF-α)和白介素6(IL-6)水平明显降低，超氧化物歧化酶(SOD)活性显著升高。此外，ALDH2、沉默信息调节因子2相关酶I(Sirt1)和核因子红系相关因子2(Nrf2)的表达显著增加，而血管内皮生长因子-α(VEGF-α)的表达显著降低。
Aims: Acetaldehyde dehydrogenase 2 (ALDH2) was reported for its protective properties on myocardial damage, stroke and neurodegeneration disease, but the effects and mechanisms of ALDH2 in the modulation of diabetic retinopathy remain unclear. The present study evaluated the protection effects of ALDH2 on streptozocin (STZ)-induced aged diabetic rats retinas damage.Main methods: 24 aged male diabetic Sprague-Dawley (SD) rats induced by a single intraperitoneal injection of STZ were randomly divided into Alda1-treated group and dimethylsulfoxide (DMSO) group. Rats were intraperitoneally injected with 10 mg/kg ALDH2 activator Alda1 (or DMSO) 3 days before STZ injection and 30 days afterwards. A series of detections on retinal structural, functional and molecular levels were applied at 1 d, 7 d and 30 d after aged diabetic rats model established.Key findings: Optical coherence tomography (OCT) revealed that the thickness of outer nuclear layer (ONL) and whole retinas in Alda1-treated group were thicker than DMSO group. Full field electroretinograms (ffERG) showed a higher amplitude wave (dark-adaptation 3.0 and OPs) in Alda1-treated group. In addition, the levels of retinal tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) from Alda1-treated group were lower whereas superoxide dismutase (SOD) activity was notably higher. Moreover, the expressions of ALDH2, silence information regulation factor 2 related enzyme I (Sirt1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in Aldal-treated group retinas were significantly increased, while the expression of vascular endothelial growth factor (VEGF-alpha) was dramatically decreased.Significance: ALDH2 could ameliorate early-stage STZ-induced aged diabetic rats retinas damage possibly via increasing Sirt1 and Nrf2 expression.