脑缺血再灌注损伤（CIRI）是一种常见的神经系统疾病，其特征是缺血再灌注过程中诱导的氧化应激和炎症反应，导致脑细胞严重损伤。人参皂苷 Rb1 是一种天然药用成分，具有潜在的神经保护作用。本研究旨在探讨人参皂苷Rb1在CIRI中的作用机制及其对脑损伤的保护作用。我们采用小鼠CIRI模型，将小鼠随机分为对照组、CIRI组和人参皂苷Rb1治疗组。通过氯化三苯基四氮唑(TTC)染色、末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色、实时逆转录酶染色观察Rb1对CIRI小鼠脑组织损伤、细胞凋亡、炎症因子表达及焦亡细胞数量的影响。转录聚合酶链反应（qRT-PCR）和电子显微镜。在细胞模型中，Rb1 通过核呼吸因子 2/肿瘤坏死因子-α (TNF-α) 诱导的蛋白 3 (TNFAIP3) 对氧糖剥夺/再灌注 (OGD/R) 诱导的 HT22 细胞焦亡的调节作用使用Western blot和TUNEL染色检测A20）/真核翻译延伸因子1A2（Nrf2/A20/eEF1A2）轴。此外，还评估了 Nrf2 抑制剂 ML385 和 eEF1A2 过表达对 Rb1 神经保护作用的影响。利用上述综合实验方法，全面评估了 Rb1 在 CIRI 中的神经保护机制。我们的研究结果表明，人参皂苷 Rb1 治疗可减轻 CIRI 引起的行为缺陷，并减少脑组织的病理损伤。此外，人参皂苷 Rb1 治疗显着降低了 CIRI 诱导的氧化应激和炎症反应，从而降低了炎症因子水平 (p < 0.05)。进一步的实验结果表明，人参皂苷Rb1通过调节Nrf2/A20/eEF1A2轴的活性来促进抗氧化和抗炎反应。此外，人参皂苷Rb1抑制NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体的激活，从而减少炎症因子的释放和细胞凋亡的发生。我们的研究结果表明，人参皂苷Rb1发挥神经保护作用，减轻炎症反应。 CIRI 通过调节 Nrf2/A20/eEF1A2 轴并抑制 NLRP3 炎症小体的激活诱导脑损伤。这些发现为CIRI提供了新的治疗见解，并支持人参皂苷Rb1作为治疗药物的开发。然而，尽管我们的研究结果充满希望，但仍需要进一步的研究来验证这些发现并探索人参皂苷 Rb1 在临床应用中的可行性和安全性。我们希望我们的研究能够为CIRI的治疗和预防提供新的方向和策略，为神经保护药物的研发做出贡献。

Cerebral ischemia-reperfusion injury (CIRI) is a prevalent neurological disorder, characterized by the oxidative stress and inflammatory response induced during the ischemia-reperfusion process, leading to significant damage to brain cells. Ginsenoside Rb1, a natural medicinal ingredient, possesses potential neuroprotective effects. This study aims to investigate the mechanism of action of ginsenoside Rb1 in CIRI and its protective effects on brain injury.We utilized a mouse CIRI model and randomly divided the mice into control group, CIRI group, and ginsenoside Rb1 treatment group. The effects of Rb1 on brain tissue damage, apoptosis, expression of inflammatory factors, and pyroptotic cell numbers in CIRI mice were observed through triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, real-time reverse transcription polymerase chain reaction (qRT-PCR), and electron microscopy. In a cell model, the regulatory effect of Rb1 on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell pyroptosis via the nuclear respiratoty factor 2/tumor necrosis factor-α (TNF-α)-induced Protein 3 (TNFAIP3, aka A20)/eukaryotic translation elongation factor 1A2 (Nrf2/A20/eEF1A2) axis was detected using Western blot and TUNEL staining. Additionally, the impact of Nrf2 inhibitor ML385 and eEF1A2 overexpression on the neuroprotective effect of Rb1 was assessed. Using the comprehensive experimental methods mentioned above, the neuroprotective mechanism of Rb1 in CIRI was thoroughly evaluated.Our findings demonstrate that treatment with ginsenoside Rb1 alleviated behavioral deficits induced by CIRI and reduced pathological damage in brain tissue. Furthermore, ginsenoside Rb1 treatment notably decreased oxidative stress and the inflammatory response induced by CIRI, leading to lower levels of inflammatory factors (p < 0.05). Further experimental results indicated that ginsenoside Rb1 promoted antioxidant and anti-inflammatory responses by regulating the activity of the Nrf2/A20/eEF1A2 axis. Additionally, ginsenoside Rb1 inhibited the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby reducing the release of inflammatory factors and the occurrence of cell apoptosis.Our study results suggest that ginsenoside Rb1 exerts neuroprotective effects and alleviates brain injury induced by CIRI by regulating the Nrf2/A20/eEF1A2 axis and inhibiting the activation of the NLRP3 inflammasome. These findings provide new treatment insights for CIRI and support ginsenoside Rb1's development as a therapeutic drug. However, despite the promising nature of our findings, further research is required to validate these discoveries and explore the feasibility and safety of ginsenoside Rb1 in clinical applications. We hope that our study can provide new directions and strategies for the treatment and prevention of CIRI, contributing to the development of neuroprotective drugs.