Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, China; The First Affiliated Hospital of Xinxiang Medical University, China; Henan Key Lab of Biological Psychiatry, Henan International Joint Laboratory of Psychiatry and Neuroscience, Xinxiang Medical University, China.
Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, China; Henan Key Lab of Biological Psychiatry, Henan International Joint Laboratory of Psychiatry and Neuroscience, Xinxiang Medical University, China.
Brain Res Bull. 2021 Aug;173:74-81. doi: 10.1016/j.brainresbull.2021.05.008. Epub 2021 May 12.
Increasing evidence suggests that oxidative damage and neuroinflammation play a critical role in the pathogenesis of post-stroke depression (PSD). These pathologic processes are tightly regulated by the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. The synthetic triterpenoid, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im), is a potent Nrf2 activator. This study investigated whether CDDO-Im exhibited antidepressant-like activity and elucidated its protective mechanisms in a rat model of PSD, which was produced by middle cerebral artery occlusion (MCAO) followed by 28 days of chronic unpredictable mild stress (CUMS) in conjunction with solitary housing. The results demonstrated that CDDO-Im treatment markedly improved the depressive-like behaviors and reduced neuronal cell loss in the hippocampus, through decreasing the malondialdehyde (MDA) content (indicative of lipid peroxidation), superoxide dismutase (SOD), NF-kB activation, interleukin-6 (IL-6) and interleukin-1b (IL-1β) in PSD rats. CDDO-Im treatment alleviated the oxidative stress and inflammatory response in PSD rats by promoting Nrf2 nuclear import and increasing the protein levels of Nrf2 downstream target genes, including heme oxygenase-1(HOMX1) and, quinone oxidoreductase-1(NQO1).These findings suggested that CDDO-Im treatment exhibited antidepressant-like effects and protected PSD rats from oxidative and inflammatory injury via the Nrf2/ARE pathway. Therefore, CDDO-Im treatment is worthy of further study.
越来越多的证据表明，氧化损伤和神经炎症在卒中后抑郁（PSD）的发病机制中起关键作用。这些病理过程受到核因子红细胞 2 相关因子 2/抗氧化反应元件（Nrf2/ARE）信号通路的严格调控。合成三萜类化合物 2-氰基-3,12-二氧代齐墩果-1,9-二烯-28-亚胺（CDDO-Im）是一种有效的 Nrf2 激活剂。本研究探讨了 CDDO-Im 是否表现出抗抑郁样活性，并阐明了其在 PSD 大鼠模型中的保护机制，该模型是通过大脑中动脉闭塞（MCAO）后 28 天慢性不可预测轻度应激（CUMS）与独居相结合产生的。结果表明，CDDO-Im 治疗通过降低丙二醛（MDA）含量（提示脂质过氧化）、超氧化物歧化酶（SOD）、核因子 kappa B（NF-kB）激活、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β），显著改善 PSD 大鼠的抑郁样行为并减少海马神经元细胞丢失。CDDO-Im 治疗通过促进 Nrf2 核输入和增加 Nrf2 下游靶基因的蛋白水平，包括血红素加氧酶-1（HOMX1）和醌氧化还原酶-1（NQO1），减轻 PSD 大鼠的氧化应激和炎症反应。这些发现表明，CDDO-Im 治疗通过 Nrf2/ARE 通路表现出抗抑郁样作用，并保护 PSD 大鼠免受氧化和炎症损伤。因此，CDDO-Im 治疗值得进一步研究。
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