Gao Fei, Wu Xiao, Mao Xiang, Niu Fei, Zhang Bin, Dong Jinqian, Liu Baiyun
Beijing Tiantan Hospital, Capital Medical University Beijing, 100070, China.
Department of Emergency, The First Affiliated Hospital of Anhui Medical University Hefei 230022, Anhui, China.
Am J Transl Res. 2021 Mar 15;13(3):1483-1493. eCollection 2021.
Astaxanthin (ATX) is a carotenoid pigment with effective antioxidant, anti-inflammatory, antitumor and immunomodulatory actions. ATX has been proposed to exert neuroprotective effects and attenuate oxidative stress in mice after traumatic brain injury (TBI). The nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway is stimulated after TBI and activates a compensatory mechanism against TBI. Nevertheless, the effect of ATX on the pathophysiology of TBI in mice is limited. Our present study evaluated the neuroprotection afforded by ATX and the possible role of the Nrf2/HO-1 pathway in experimental TBI.
Mice were casually separated into 3 groups: the sham, TBI + vehicle, and TBI + ATX (100 mg/kg, intraperitoneally administered) groups. Neurobehaviors of the mice were assessed using the neurological severity scores (NSSs), the forced swimming test (FST) and the rotarod test. Levels of the Nrf2, HO-1, NAD(P)H: quinine oxidoreductase-1 (NQO1), cleaved caspase3 (C-caspase3), and superoxide dismutase1 (SOD1) proteins and levels of the Nrf2 and HO-1 mRNAs were assessed. In addition, Nrf2 nuclear import and apoptosis were measured after TBI.
The ATX treatment significantly improved the neurological status, promoted Nrf2 activation, and upregulated the expression of the Nrf2 and HO-1 mRNAs and the levels of the Nrf2, HO-1, and NQO1 proteins after TBI. The level of the SOD1 protein was decreased after TBI and increased after ATX treatment; however, the difference was not significant. ATX markedly reduced the level of the C-caspase3 protein and the number of TUNEL-positive cells, indicating that it exerted an antiapoptotic effect. Immunofluorescence staining confirmed that ATX promoted Nrf2 nuclear import.
Based on our study, ATX possibly affords neuroprotection by activating the Nrf2/HO-1 signaling pathway in mice after TBI.
虾青素（ATX）是一种类胡萝卜素色素，具有有效的抗氧化、抗炎、抗肿瘤和免疫调节作用。有人提出ATX对创伤性脑损伤（TBI）后的小鼠具有神经保护作用并减轻氧化应激。核因子红细胞2相关因子2（Nrf2）-血红素加氧酶1（HO-1）信号通路在TBI后被激活，并启动针对TBI的代偿机制。然而，ATX对小鼠TBI病理生理学的影响有限。我们目前的研究评估了ATX提供的神经保护作用以及Nrf2/HO-1通路在实验性TBI中的可能作用。
将小鼠随机分为3组：假手术组、TBI + 载体组和TBI + ATX（100 mg/kg，腹腔注射）组。使用神经严重程度评分（NSS）、强迫游泳试验（FST）和转棒试验评估小鼠的神经行为。评估Nrf2、HO-1、NAD(P)H：醌氧化还原酶-1（NQO1）、裂解的半胱天冬酶3（C-半胱天冬酶3）和超氧化物歧化酶1（SOD1）蛋白水平以及Nrf2和HO-1 mRNA水平。此外，在TBI后测量Nrf2核转运和细胞凋亡。
ATX治疗显著改善了神经状态，促进了Nrf2激活，并上调了TBI后Nrf2和HO-1 mRNA的表达以及Nrf2、HO-1和NQO1蛋白的水平。TBI后SOD1蛋白水平降低，ATX治疗后升高；然而，差异不显著。ATX显著降低了C-半胱天冬酶3蛋白水平和TUNEL阳性细胞数量，表明其具有抗凋亡作用。免疫荧光染色证实ATX促进了Nrf2核转运。
基于我们的研究，ATX可能通过激活TBI后小鼠的Nrf2/HO-1信号通路提供神经保护作用。
