Docosahexaenoic acid (DHA) is verified to have neuroprotective effects on traumatic brain injury (TBI) rats by activating Nrf2 signaling pathway, but the role of NOX₂ in this effect has not been illuminated. So this study explored the role of NOX₂ in TBI models treated with DHA, aiming to complete the mechanism of DHA. TBI rat models were constructed with or without DHA treatment, and H₂O₂-induced hippocampal neurons were pretreated with DHA alone or in combination with Nrf2 inhibitor brusatol. The neurological function, cognitive ability, and cerebral edema degree of rats were assessed. The apoptosis rate and viability of cells was measured. The generation of NOX₂, Nrf2, HO-1 and NQO-1 expression levels, and ROS content in hippocampal CA1 region and hippocampal neurons were detected. DHA could not only improve the neurological function, brain edema and cognitive ability in TBI rats, but also decrease effectively the contents of NOX₂ and ROS in hippocampal CA1 region and hippocampal neurons. DHA promoted the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal CA1 region and hippocampal neurons. On the contrary, Nrf2 inhibitor brusatol inhibited the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal neurons, promoted the generation of ROS and NOX₂, and accelerated cell apoptosis. Both in vivo and in vitro experiments demonstrated that DHA treated TBI by reducing NOX₂ generation that might function on Nrf2 signaling pathway, providing a potential evidence for its clinical application.

二十二碳六烯酸（DHA）被证实通过激活Nrf2信号通路对创伤性脑损伤（TBI）大鼠具有神经保护作用，但NOX ₂在该作用中的作用尚未阐明。因此本研究探讨NOX ₂在DHA治疗TBI模型中的作用，旨在完善DHA的作用机制。构建有或没有DHA处理的TBI大鼠模型，并用单独的DHA或与Nrf2抑制剂brusatol联合预处理H ₂ O ₂诱导的海马神经元。评估大鼠的神经功能、认知能力和脑水肿程度。测量细胞的凋亡率和活力。检测海马CA1区及海马神经元NOX ₂ 、Nrf2、HO-1、NQO-1表达水平以及ROS含量。 DHA不仅可以改善TBI大鼠的神经功能、脑水肿和认知能力，而且可以有效降低海马CA1区和海马神经元中NOX ₂和ROS的含量。 DHA促进Nrf2核转位以及海马CA1区和海马神经元HO-1和NQO-1的表达水平。相反，Nrf2抑制剂布鲁萨醇抑制海马神经元Nrf2的核转位及HO-1和NQO-1的表达水平，促进ROS和NOX ₂的生成，加速细胞凋亡。体内和体外实验均表明，DHA通过减少可能在Nrf2信号通路上发挥作用的NOX ₂的产生来治疗TBI，为其临床应用提供了潜在的证据。