无机硝酸盐通过唾液酸转运蛋白减轻创伤性脑损伤后的神经炎症。
Inorganic nitrate attenuates neuroinflammation after traumatic brain injury via Sialin.
作者信息
Liu Zanxu, Hu Liang, Wang Qiaochu, Zhao Xiang, Liu Weiming, Zhang Bin, Pan Wen, Song Wenpeng, Chen Xi, Zhang Chunmei, Wang Jinsong, Wang Songlin, Zhou Jian
机构信息
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing 100069, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing 100069, China; Department Head, Outpatient Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing 100070, China.
出版信息
Tissue Cell. 2025 Oct;96:102955. doi: 10.1016/j.tice.2025.102955. Epub 2025 May 10.
BACKGROUND
Traumatic brain injury (TBI) is a significant concern in neurosurgery due to its severe consequences. Neuroinflammation is a critical response following the initial brain insult, leading to cumulative neuronal damage and chronic neurodegeneration, with limited effective treatments available. Inorganic nitrate, an essential nutrient known for its anti-inflammatory properties, is widely utilized in disease prevention and treatment. This study investigated the short-term effects of inorganic nitrate on neuroinflammation and explored the role of Sialin in neuroprotection during the early phase post-TBI.
METHODS
Male C57BL/6 mice underwent TBI using an electrically controlled cortical impactor (eCCI) model. Animals were administered nitrate or sterile saline intragastrically twice daily for 1,3 or 7 days post-injury (dpi) until sacrifice. Neurobehavioral function was evaluated, and brain tissues were collected for morphological, histopathological, and molecular analyses.
RESULTS
Nitrate enhanced neurobehavioral function recovery and improved neurological outcomes at 3 dpi. While nitrate did not significantly reduce structural damage, it did decrease neuronal loss and apoptosis in the early stages of TBI. RNA-seq of injured brains at 3 dpi revealed more genes and signaling pathways linked to immune processes following early nitrate treatment compared to the vehicle, indicating inflammation inhibition. This was further confirmed at the mRNA and protein levels. Specifically, key gene markers of inflammatory mediators were notably suppressed by early nitrate compared to the corresponding TBI vehicle groups. However, the knockdown of Slc17a5 reduced the effectiveness of nitrate on short-term neurobehavior in TBI mice and nullified its anti-inflammatory effects.
CONCLUSION
Inorganic nitrate can improve neurological outcomes and attenuate neuroinflammation following TBI, attributed in part to the normalisation of the inflammatory response mediated by Sialin. The discovery lays a promising groundwork for the protective effects of nitrate in TBI conditions.
背景
创伤性脑损伤（TBI）因其严重后果而成为神经外科领域的重大关注点。神经炎症是脑损伤后的关键反应，会导致累积性神经元损伤和慢性神经退行性变，而有效的治疗方法有限。无机硝酸盐作为一种以抗炎特性闻名的必需营养素，被广泛用于疾病预防和治疗。本研究调查了无机硝酸盐对神经炎症的短期影响，并探讨了唾液酸转运蛋白（Sialin）在TBI后早期神经保护中的作用。
方法
雄性C57BL/6小鼠采用电控皮质撞击器（eCCI）模型造成TBI。受伤后1、3或7天（dpi），每天两次给动物灌胃硝酸盐或无菌生理盐水，直至处死。评估神经行为功能，并收集脑组织进行形态学、组织病理学和分子分析。
结果
在3 dpi时，硝酸盐可促进神经行为功能恢复并改善神经学结果。虽然硝酸盐并未显著减少结构损伤，但它确实减少了TBI早期阶段的神经元丢失和凋亡。与载体组相比，3 dpi时受伤大脑的RNA测序显示，早期硝酸盐处理后与免疫过程相关的基因和信号通路更多，表明炎症受到抑制。这在mRNA和蛋白质水平上得到了进一步证实。具体而言，与相应的TBI载体组相比，早期硝酸盐显著抑制了炎症介质的关键基因标志物。然而，敲低Slc17a5会降低硝酸盐对TBI小鼠短期神经行为的有效性，并消除其抗炎作用。
结论
无机硝酸盐可改善TBI后的神经学结果并减轻神经炎症，部分原因是唾液酸转运蛋白介导的炎症反应正常化。这一发现为硝酸盐在TBI情况下的保护作用奠定了有前景的基础。
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