补阳还五汤对低压低氧诱导的小鼠脑损伤的保护作用及机制：涉及炎症反应和HIF-1/PI3K-Akt相关通路
Protective effect and mechanisms of Buyang Huanwu decoction against hypobaric hypoxia-induced brain injury in mice: involvement of inflammatory responses and HIF-1/PI3K-Akt-related pathways.
摘要(中文译文)
本研究旨在探讨补阳还五汤(Buyang Huanwu Decoction, BHD)对低压低氧诱导的小鼠脑损伤的预防和保护作用,并探究其潜在机制。研究特别着重评估BHD预处理能否预防或减轻低压低氧诱导的神经功能障碍和海马损伤,并从炎症反应、代谢调节及HIF-1/PI3K-Akt相关通路的角度阐明其潜在机制。通过暴露于相当于海拔6000 m的模拟高原低氧环境72 h,建立低压低氧诱导脑损伤的小鼠模型。小鼠被分为正常对照组、模型组、BHD预处理组和乙酰唑胺阳性对照组。BHD和乙酰唑胺自低压低氧暴露前4天开始每日灌胃给药一次,并在72 h暴露期间持续给药。采用旷场实验评估自发运动活动和探索行为。通过苏木精-伊红染色、尼氏染色和HIF-1α免疫荧光染色评估海马损伤。整合非靶向血清代谢组学、网络药理学、海马转录组学和RT-qPCR验证,探究BHD预处理的潜在机制。BHD预处理可预防低压低氧诱导的行为异常,并减轻海马病理损伤、神经元丢失和尼氏体减少。BHD还可降低海马HIF-1α的过度表达。多组学分析提示,BHD的保护作用与调节炎症反应、代谢紊乱及HIF-1/PI3K-Akt相关信号有关。RT-qPCR验证显示,BHD可调节海马组织中HIF-1α、IL-6、VEGFA、NF-κB1和STX1A的异常表达。BHD对低压低氧诱导的小鼠脑损伤发挥预防性神经保护作用。其作用可能涉及对低氧反应、炎症信号、代谢重塑及HIF-1/PI3K-Akt相关通路的协同调节。
Abstract
This study aimed to investigate the preventive and protective effect of Buyang Huanwu Decoction (BHD) against hypobaric hypoxia-induced brain injury in mice and to explore its underlying mechanisms. Particular emphasis was placed on evaluating whether BHD pretreatment could prevent or attenuate hypobaric hypoxia-induced neurological dysfunction and hippocampal injury, and on clarifying its potential mechanisms from the perspectives of inflammatory responses, metabolic regulation, and HIF-1/PI3K-Akt-related pathways. A mouse model of hypobaric hypoxia-induced brain injury was established by exposure to a simulated high-altitude hypoxic environment equivalent to an altitude of 6000 m for 72 h. Mice were assigned to the normal control, model, BHD-pretreated, and acetazolamide-positive control groups. BHD and acetazolamide were administered once daily by intragastric gavage, starting 4 days before hypobaric hypoxia exposure and continuing during the 72 h exposure period. Open field testing was performed to assess spontaneous locomotor activity and exploratory behavior. Hippocampal injury was evaluated by hematoxylin and eosin staining, Nissl staining, and HIF-1α immunofluorescence staining. Non-targeted serum metabolomics, network pharmacology, hippocampal transcriptomics, and RT-qPCR validation were integrated to explore the potential mechanisms of BHD pretreatment. BHD pretreatment prevented hypobaric hypoxia-induced behavioral abnormalities and alleviated hippocampal pathological injury, neuronal loss, and Nissl body reduction. BHD also reduced excessive hippocampal HIF-1α expression. Multi-omics analyses suggested that the protective effect of BHD was associated with the regulation of inflammatory responses, metabolic disturbances, and HIF-1/PI3K-Akt-related signaling. RT-qPCR validation showed that BHD modulated the abnormal expression of HIF-1α, IL-6, VEGFA, NF-κB1, and STX1A in hippocampal tissue. BHD exerts a preventive neuroprotective effect against hypobaric hypoxia-induced brain injury in mice. Its effects may involve coordinated regulation of hypoxic responses, inflammatory signaling, metabolic remodeling, and HIF-1/PI3K-Akt-related pathways.
如何引用
AMA
Zhixing Wang, Bowei Li, Xin Shen, Baoying Shen, Chunqi Yang, Lijun Huang, et al. Protective effect and mechanisms of Buyang Huanwu decoction against hypobaric hypoxia-induced brain injury in mice: involvement of inflammatory responses and HIF-1/PI3K-Akt-related pathways.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1856864.
APA
Zhixing Wang, Bowei Li, Xin Shen, Baoying Shen, Chunqi Yang, Lijun Huang, et al (2026). Protective effect and mechanisms of Buyang Huanwu decoction against hypobaric hypoxia-induced brain injury in mice: involvement of inflammatory responses and HIF-1/PI3K-Akt-related pathways.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1856864
GB/T 7714
Zhixing Wang, Bowei Li, Xin Shen, Baoying Shen, Chunqi Yang, Lijun Huang, et al. Protective effect and mechanisms of Buyang Huanwu decoction against hypobaric hypoxia-induced brain injury in mice: involvement of inflammatory responses and HIF-1/PI3K-Akt-related pathways.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1856864.
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