Abstract：
C1q/tumor necrosis factor-related protein-9 (CTRP9) is linked to diverse pathological conditions via the effects on cell apoptosis, inflammatory response, and oxidative stress. However, its functional relevance in ischemic brain injury is not well determined. The present work aimed to evaluate the role of CTRP9 in ischemia/reperfusion-associated neuronal injury using an in vitro model. The cultured cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate ischemia/reperfusion in vitro. CTRP9 level was lowered in cultured neurons exposed to OGD/R. Neurons with overexpressed CTRP9 were resistant to OGD/R-elicited injuries, including neuronal apoptosis, oxidative stress, and pro-inflammatory response. Mechanism research revealed that CTRP9 could boost the activation of the nuclear factor erythroid 2-related factor (Nrf2) pathway associated with modulation of the Akt-glycogen synthase kinase-3β (GSK-3β) axis. CTRP9 regulated the transduction of the Akt-GSK-3β-Nrf2 cascade via adiponectin receptor 1 (AdipoR1). Restraining Nrf2 could diminish CTRP9-mediated neuroprotective effects in OGD/R-injured neurons. Altogether, these results confirmed that CTRP9 exerts a protective effect on OGD/R-injured neurons by modulating Akt-GSK-3β-Nrf2 cascade via AdipoR1. This work suggests a possible link between CTRP9 and ischemic brain injury.
摘要：
C1q/肿瘤坏死因子相关蛋白-9（CTRP9）通过对细胞凋亡的影响与多种病理状况有关，炎症反应，和氧化应激。然而,其在缺血性脑损伤中的功能相关性尚不明确。本工作旨在使用体外模型评估CTRP9在缺血/再灌注相关神经元损伤中的作用。对培养的皮质神经元进行氧糖剥夺/复氧（OGD/R）以模拟体外缺血/再灌注。暴露于OGD/R的培养神经元中CTRP9水平降低。CTRP9过表达的神经元对OGD/R引起的损伤具有抗性，包括神经元凋亡，氧化应激，和促炎反应。机制研究表明，CTRP9可以促进与Akt-糖原合酶激酶3β（GSK-3β）轴调节相关的核因子红系2相关因子（Nrf2）途径的激活。CTRP9通过脂联素受体1(AdipoR1)调节Akt-GSK-3β-Nrf2级联的转导。抑制Nrf2可以减少CTRP9介导的OGD/R损伤神经元的神经保护作用。总之,这些结果证实CTRP9通过通过AdipoR1调节Akt-GSK-3β-Nrf2级联对OGD/R损伤的神经元具有保护作用。这项工作表明CTRP9与缺血性脑损伤之间可能存在联系。
