【摘要】 目的：探讨刺五加抗高原脑水肿（HACE）的活性成分及药理机制。方法：采用UHPLC-LTQ-Orbitrap-MS技术对刺五加的化学成分进行综合分析；应用网络药理学，分析刺五加抗HACE的潜在活性成分和可能的药理机制；复制HACE大鼠模型，通过测定脑含水量和蛋白印迹法检测PI3K/Akt信号通路表达，验证刺五加抗HACE的药理机制。结果：通过UHPLC-LTQ-Orbitrap-MS筛选出刺五加的30个化学成分。通过网络药理学，得到106个成分与疾病的交集靶点。PPI网络中显示了Akt1、HIF1A、TNF、ALB、BCL2等关键靶点，GO和KEGG通路富集分析表明刺五加苷B的抗HACE作用可能与PI3K/Akt信号通路有关，分子对接结果显示刺五加苷B与Akt1蛋白之间存在良好的相互作用。脑含水量分析显示刺五加苷B降低脑含水量，减轻脑组织损伤。Western blot实验表明，刺五加苷B预处理后，p-PI3K和p-Akt的表达增加，而PI3K抑制剂阻断了PI3K/Akt信号通路并逆转了刺五加苷B的作用。结论：刺五加对HACE的保护作用主要是通过PI3K/Akt途径介导的。更多还原

【Abstract】 Objective: This work aims to explore the active ingredients and pharmacological mechanisms of Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis(Ciwujia)against high altitude cerebral edema(HACE). Methods: The ingredients of Ciwujia were comprehensively analyzed using UHPLC-LTQ-Orbitrap-MS method. Network pharmacology was applied to decipher the potential active ingredients and pharmacological mechanisms of Ciwujia against HACE. Animal experiments were conducted using the HACE rat model. Initially, brain water content was measured, and then, the expression of the PI3K/AKT signaling pathway was detected by Western blot to verify the pharmacological mechanism of Ciwujia against HACE. Results: A total of 30 constituents of Ciwujia were identified via UHPLC-LTQ-Orbitrap-MS. Through network pharmacology, 106 intersecting targets between components and diseases were identified. Key targets, such as AKT1, HIF1A, TNF, ALB, BCL2 were shown in PPI network. GO and KEGG pathway enrichment analysis suggested that the anti HACE effect of eleutheroside B may be related to the PI3K/Akt signaling pathway.Molecular docking suggested that there was good interaction between eleutheroside B and Akt1 protein. Brain water content analysis showed that eleutheroside B reduced brain water content and alleviated brain tissue damage. Western blot showed that pretreatment with eleutheroside B increased the expression of p-PI3K and p-Akt. A PI3K inhibitor blocked the PI3K/Akt signaling pathway and reversed the effects of eleutheroside B. Conclusion: The protective effect of Ciwujia against HACE was mainly mediated through the PI3K/Akt pathway.更多还原