Department of Neurosurgery, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan 453000, PR China.
Department of Neurosurgery, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan 453000, PR China.
J Stroke Cerebrovasc Dis. 2024 Nov;33(11):107950. doi: 10.1016/j.jstrokecerebrovasdis.2024.107950. Epub 2024 Aug 20.
Oxidative stress and neuroapoptosis are significant pathological processes that occur in response to intracerebral hemorrhage (ICH), however, the optimal therapeutic strategy to treat these responses remains unknown. Pterostilbene (PTE) influences neural cell survival in in the pathology of a number of neurological diseases, but the mechanisms underlying this influence at present are not clear. The objective of the present study was to examine the potential impact of PTE on mitigating oxidative stress and neuronal apoptosis following ICH, while also elucidating the potential underlying pathways.
MATERIAL & METHOD: For in vivo experimentation, male C57BL/6 mice were used to establish ICH models. Wet-to-dry weight ratios were utilized to assess the degree of cerebral edema in the context of PTE intervention. Behavioral experiments were conducted to evaluate neurological dysfunction and cognitive impairment, and hematoxylin and eosin staining was employed to observe histopathological changes in the brain. Furthermore, oxidative stress levels in hippocampal tissues were measured, and cell apoptosis was examined using TUNEL staining and western blotting techniques. In vitro experiments were conducted to evaluate the extent of oxidative stress and neural apoptosis after sirtuin 1 (SIRT1) siRNA treatment. Immunofluorescence cytochemistry was used to analyze the immunofluorescence colocalization of SIRT1 and NeuN.
Mice that experienced ICH exhibited worsening neurological deterioration, increased oxidative stress and neuronal cell apoptosis. However, the addition of PTE was found to lessen these effects. Furthermore, PTE was found to activate the SIRT1-mediated Nrf2 pathway in mice with ICH. When SIRT1 was inhibited, levels of oxidative stress and neuronal apoptosis increased, even in the presence of PTE.
The present study provided evidence to indicate that PTE can suppress oxidative damage and neuronal apoptosis following ICH by activating the SIRT1/Nrf2 pathway.
氧化应激和神经细胞凋亡是脑出血（ICH）后发生的重要病理过程，然而，治疗这些反应的最佳治疗策略仍不清楚。紫檀芪（PTE）影响许多神经疾病的神经细胞存活，但目前尚不清楚这种影响的潜在机制。本研究旨在研究 PTE 对减轻 ICH 后氧化应激和神经元细胞凋亡的潜在影响，并阐明潜在的作用途径。
体内实验采用雄性 C57BL/6 小鼠建立 ICH 模型。采用干湿重比评估 PTE 干预时脑水肿的程度。进行行为实验评估神经功能障碍和认知障碍，并用苏木精-伊红染色观察脑的组织病理学变化。此外，还测量了海马组织中的氧化应激水平，并通过 TUNEL 染色和 Western blot 技术检测细胞凋亡。体外实验评估 SIRT1 （SIRT1） siRNA 处理后氧化应激和神经细胞凋亡的程度。免疫荧光细胞化学分析 SIRT1 和 NeuN 的免疫荧光共定位。
发生 ICH 的小鼠表现出神经功能恶化加重、氧化应激增加和神经元细胞凋亡。然而，添加 PTE 可减轻这些影响。此外，研究发现 PTE 可激活 ICH 小鼠中的 SIRT1 介导的 Nrf2 途径。当抑制 SIRT1 时，即使存在 PTE，氧化应激和神经元细胞凋亡水平也会增加。
本研究提供的证据表明，PTE 通过激活 SIRT1/Nrf2 途径可以抑制 ICH 后氧化损伤和神经元细胞凋亡。
