背景:脑缺血再灌注损伤(CIRI)是一种常见的神经系统疾病,以缺血再灌注过程中诱导的氧化应激和炎症反应为特征,导致脑细胞严重受损。人参皂苷Rb1,一种天然药用成分,具有潜在的神经保护作用。本研究旨在探讨人参皂苷Rb1inCIRI的作用机制及其对脑损伤的保护作用。
方法:我们使用小鼠CIRI模型,将小鼠随机分为对照组,CIRI组,人参皂苷Rb1治疗组。Rb1对脑组织损伤的影响,凋亡,炎症因子的表达,并通过氯化三苯基四唑(TTC)染色观察CIRI小鼠的焦变细胞数,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,akaA20)/真核翻译延伸因子1A2(Nrf2/A20/eEF1A2)轴对氧葡萄糖剥夺/再灌注(OGD/R)诱导的HT22细胞凋亡的调节作用使用Westernblot和TUNEL染色检测。此外,评估了Nrf2抑制剂ML385和eEF1A2过表达对Rb1神经保护作用的影响.采用上述综合实验方法,对Rb1inCIRI的神经保护机制进行了全面评估。
结果:我们的发现表明,人参皂苷Rb1治疗减轻了CIRI引起的行为缺陷,并减少了脑组织的病理损伤。此外,人参皂苷Rb1治疗显著降低氧化应激和CI诱导的炎症反应,导致炎症因子水平降低(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)炎性小体的活化,从而减少炎症因子的释放和细胞凋亡的发生。
结论:我们的研究结果表明,人参皂苷Rb1具有神经保护作用,并通过调节Nrf2/A20/eEF1A2轴并抑制NLRP3炎性体的激活来减轻CIRI引起的脑损伤。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,尽管我们的发现很有希望,需要进一步的研究来验证这些发现,并探讨人参皂苷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。促进神经保护药物的发展。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.