Huang Yuxing, He Yijia, Zhao Xiaolong, Zou Yongjie, Ding Weijun, Wei Linjie
Department of Neurosurgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Neurochem Res. 2025 Jun 21;50(4):204. doi: 10.1007/s11064-025-04430-x.
Traumatic brain injury (TBI) carries a high incidence of morbidity and mortality worldwide. We aim to explore the neuroprotective effects of Salidroside (Sal) on TBI and the specific mechanisms involved. The controlled cortical impact (CCI) was adopted to induce TBI in mice. Mice were randomly divided into the following groups: Sham group, TBI group, low-dose Sal (Sal-L) group, High-dose Sal (Sal-H) group and the Ferrostatin-1 (Fer) group. Neurological function of mice was assessed by Neurological Severity Score and behavioral tests, with Hematoxylin-eosin and Nissl staining for histological analysis. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay was employed to detect neuronal apoptosis. Evans blue extravasation was observed to assess blood-brain barrier (BBB) permeability. Immunohistochemistry detected the astrocyte and microglial markers. Remyelination was evaluated by immunofluorescent labeling of myelin basic protein and Luxol Fast Blue staining. Reactive oxygen species (ROS), malondialdehyde, and glutathione levels were detected to assess lipid peroxidation. Ferroptosis was accessed by Prussian blue staining and western blot. Sal improved neurological deficits, reduced histopathological damage, inhibited neuronal apoptosis, and maintained neuronal structural stability in TBI mice. Sal downregulated the expression of Glial Fibrillary Acidic Protein (GFAP) and Iba1, indicating the suppression of astrocyte and microglia activation. Additionally, Sal alleviated BBB damage and promoted myelin regeneration. Sal treatment caused a decrease in ROS and malondialdehyde (MDA), while an increase in glutathione. Notably, Sal exhibited inhibitory effects on ferroptosis, as evidenced by reduced iron deposits, decreased iron ion levels, and modulated expression of key proteins involved in the ferroptosis, including upregulation of ferroptosis-inhibitory proteins and downregulation of ferroptosis-promoting proteins. Sal inhibits lipid peroxidation to suppress ferroptosis, thus exerting a neuroprotective effect on TBI mice.
创伤性脑损伤（TBI）在全球范围内具有很高的发病率和死亡率。我们旨在探讨红景天苷（Sal）对TBI的神经保护作用及其具体机制。采用控制性皮质撞击（CCI）法诱导小鼠TBI。将小鼠随机分为以下几组：假手术组、TBI组、低剂量Sal（Sal-L）组、高剂量Sal（Sal-H）组和铁死亡抑制剂-1（Fer）组。通过神经严重程度评分和行为测试评估小鼠的神经功能，采用苏木精-伊红染色和尼氏染色进行组织学分析。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测神经元凋亡。观察伊文思蓝外渗情况以评估血脑屏障（BBB）通透性。免疫组织化学检测星形胶质细胞和小胶质细胞标志物。通过髓鞘碱性蛋白免疫荧光标记和Luxol Fast Blue染色评估髓鞘再生情况。检测活性氧（ROS）、丙二醛和谷胱甘肽水平以评估脂质过氧化。通过普鲁士蓝染色和蛋白质印迹法评估铁死亡情况。Sal改善了TBI小鼠的神经功能缺损，减少了组织病理学损伤，抑制了神经元凋亡，并维持了神经元结构的稳定性。Sal下调了胶质纤维酸性蛋白（GFAP）和离子钙结合衔接分子1（Iba1）的表达，表明抑制了星形胶质细胞和小胶质细胞的激活。此外，Sal减轻了BBB损伤并促进了髓鞘再生。Sal处理导致ROS和丙二醛（MDA）减少，而谷胱甘肽增加。值得注意的是，Sal对铁死亡具有抑制作用，表现为铁沉积减少、铁离子水平降低以及铁死亡相关关键蛋白表达的调节，包括铁死亡抑制蛋白上调和铁死亡促进蛋白下调。Sal抑制脂质过氧化以抑制铁死亡，从而对TBI小鼠发挥神经保护作用。
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