1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a lipophilic phenolic agent, has an antioxidant activity and reactive oxygen species (ROS) scavenging property. However, the role of HTHQ on cerebral ischaemic/reperfusion (I/R) injury and the underlying mechanisms remain poorly understood. In the present study, we demonstrated that HTHQ treatment ameliorated cerebral I/R injury in vivo, as demonstrated by the decreased infarct volume ration, neurological deficits, oxidative stress and neuronal apoptosis. HTHQ treatment increased the levels of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant protein, haeme oxygenase‐1 (HO‐1). In addition, HTHQ treatment decreases oxidative stress and neuronal apoptosis of PC12 cells following hypoxia and reperfusion (H/R) in vitro. Moreover, we provided evidence that PC12 cells were more vulnerable to H/R‐induced oxidative stress after si‐Nrf2 transfection, and the HTHQ‐mediated protection was lost in PC12 cells transfected with siNrf2. In conclusion, these results suggested that HTHQ possesses neuroprotective effects against oxidative stress and apoptosis after cerebral I/R injury via activation of the Nrf2/HO‐1 pathway.

中文翻译：

---

1-O-己基-2,3,5-三甲基对苯二酚通过激活Nrf2 / HO-1途径对缺血/再灌注引起的神经元损伤的神经保护作用。

1-O-己基-2,3,5-三甲基对苯二酚（HTHQ）是一种亲脂性酚类药物，具有抗氧化活性和活性氧（ROS）清除性能。但是，HTHQ在脑缺血/再灌注（I / R）损伤中的作用及其潜在机制仍知之甚少。在本研究中，我们证明了HTHQ治疗可改善体内脑I / R损伤，如梗死体积比降低，神经功能缺损，氧化应激和神经元凋亡所证明。HTHQ治疗可增加核因子类红细胞2相关因子2（Nrf2）及其下游抗氧化蛋白血红素加氧酶-1（HO-1）的水平。此外，HTHQ处理可降低体外缺氧和再灌注（H / R）后PC12细胞的氧化应激和神经元凋亡。此外，我们提供的证据表明，在siNrf2转染后，PC12细胞更容易受到H / R诱导的氧化应激的影响，而在siNrf2转染的PC12细胞中，HTHQ介导的保护作用丧失了。总之，这些结果表明，HTHQ通过激活Nrf2 / HO-1途径对脑I / R损伤后的氧化应激和凋亡具有神经保护作用。