核因子红细胞 2 相关因子 2 激动剂可保护谷氨酸兴奋性毒性视网膜中的视网膜神经节细胞。
Nuclear factor erythroid 2-related factor 2 agonist protects retinal ganglion cells in glutamate excitotoxicity retinas.
机构信息
Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
出版信息
Biomed Pharmacother. 2022 Sep;153:113378. doi: 10.1016/j.biopha.2022.113378. Epub 2022 Jul 13.
OBJECTIVE
To investigate whether tert-Butylhydroquinone (TBHQ) can ameliorate oxidative stress and inflammation induced by glutamate excitotoxicity, and mediate retinal ganglion cell (RGC) damage by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and inhibiting the nuclear factor kappa B (NF-κB) signaling pathway.
MATERIALS AND METHODS
TBHQ was used to treat a glutamate excitotoxicity model of retinal cell line 28 and C57 mice. Damage to RGCs and visual function were assessed using flash visual evoked potential (FVEP), immunofluorescence, propidium iodide staining, and hematoxylin and eosin staining. Knockdown of Nrf2 used Nrf2 shRNA. The expression levels of related proteins were detected using western blot and immunofluorescence.
RESULTS
Glutamate excitotoxicity down-regulated Nrf2 expression in vitro and in vivo. Nuclear factor erythroid2-related factor 2 activation by TBHQ reduced the damage to retinal ganglion cells, reduced the thinning of the whole retina and the ganglion cell complex, and shortened the latency of the FVEP forward wave after injury. In addition, the levels of NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1), and Nrf2 increased significantly, and those of cyclooxygenase-2 (COX2) and NF-κB decreased significantly, after TBHQ treatment. Compared with TBHQ treatment group, the expression level of p-p65 in shRNA transfected group was increased, but still lower than that in Glu group.
CONCLUSION
The protective effect of TBHQ on RGC loss under glutamate excitotoxicity might be related to the activation of the Nrf2 signaling pathway, anti-oxidative stress, inhibition of NF-κB activation, and inhibition of retinal inflammation. Thus, TBHQ might be used to treat glutamate excitotoxicity -related retinopathy.
目的
研究叔丁基对苯二酚（TBHQ）是否可以通过激活核因子红细胞 2 相关因子 2（Nrf2）信号通路和抑制核因子 kappa B（NF-κB）信号通路来改善谷氨酸兴奋性毒性引起的氧化应激和炎症，并介导视网膜神经节细胞（RGC）损伤。
材料和方法
用 TBHQ 处理视网膜细胞系 28 及 C57 小鼠的谷氨酸兴奋性毒性模型。使用闪光视觉诱发电位（FVEP）、免疫荧光、碘化丙啶染色和苏木精和伊红染色评估 RGC 损伤和视觉功能。使用 Nrf2 shRNA 敲低 Nrf2。使用 Western blot 和免疫荧光检测相关蛋白的表达水平。
结果
谷氨酸兴奋性毒性使体外和体内的 Nrf2 表达下调。TBHQ 激活 Nrf2 可减少视网膜神经节细胞损伤，减少整个视网膜和节细胞复合体的变薄，并缩短损伤后 FVEP 前波的潜伏期。此外，TBHQ 处理后 NAD（P）H 醌脱氢酶 1（NQO1）、血红素加氧酶 1（HO-1）和 Nrf2 的水平显著增加，环氧化酶-2（COX2）和 NF-κB 的水平显著降低。与 TBHQ 处理组相比，shRNA 转染组的 p-p65 表达水平增加，但仍低于 Glu 组。
结论
TBHQ 对谷氨酸兴奋性毒性下 RGC 损失的保护作用可能与 Nrf2 信号通路的激活、抗氧化应激、抑制 NF-κB 激活和抑制视网膜炎症有关。因此，TBHQ 可能用于治疗谷氨酸兴奋性毒性相关的视网膜病变。
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