C1q / 肿瘤坏死因子相关蛋白 -9（CTRP9）通过对细胞凋亡、炎症反应和氧化应激的影响与多种病理条件相关。然而，其在缺血性脑损伤中的功能相关性尚未完全确定。本研究旨在利用体外模型评估CTRP9在缺血/再灌注相关的神经损伤中的作用。培养的皮层神经元经过氧-葡萄糖剥夺/再氧化（OGD / R）暴露于体外以模拟缺血/再灌注。CTRP9水平在经过OGD / R处理的培养神经元中降低。过表达CTRP9的神经元对OGD / R引起的损伤具有抗性，包括神经元凋亡，氧化应激和促炎症反应。机制研究表明，CTRP9可以增强与Akt-糖原合成酶激酶-3β（GSK-3β）轴调节相关的核因子肌红蛋白2相关因子（Nrf2）通路的激活。CTRP9通过脂联素受体1（AdipoR1）调节Akt-GSK-3β-Nrf2级联传导。抑制Nrf2可能减弱CTRP9介导的OGD / R受损神经元的神经保护作用。总之，这些结果确认了CTRP9通过通过AdipoR1调节Akt-GSK-3β-Nrf2级联传导在OGD / R受损神经元上发挥保护作用。本研究暗示了CTRP9与缺血性脑损伤之间可能存在的联系。 版权所有©2023 Elsevier B.V.

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.Copyright © 2023 Elsevier B.V. All rights reserved.