背景:安宫牛黄湾(AGNHW,),是传统中药(TCM)的经典药物配方,因其在缺血性脑损伤中的神经保护特性而受到赞赏,然而,其复杂的机制仍然只是部分阐明。
目的:本研究利用先进的质量细胞计数(CyTOF)深入分析AGNHW的多方面免疫调节作用,强调以前开发不足的区域。
结果:AGNHW减轻了脑中单核细胞源性巨噬细胞(MoDM)的浸润,区分其对小胶质细胞的影响。而媒介物组表现出升高的炎症标志物,如CD4,CD8a,缺血性大脑中的CD44,AGNHW治疗组减弱了它们的表达,表明AGNHW有可能缓和缺血后炎症反应。系统地,AGNHW调节基本免疫细胞动力学,特别是增强CD8+T细胞,B细胞,单核细胞,在中风后的情况下,外周血中的中性粒细胞计数。细胞内,AGNHW展示了其对信号通路的靶向调节,揭示了对关键标记如IκBα的显著抑制,提示缺血性脑损伤中炎性反应的潜在抑制。
结论:这项研究提供了AGNHW对缺血性卒中的免疫调节作用的全面描述,阐明其双重作用位点-大脑和系统-及其对细胞和分子动力学的细微调节。
BACKGROUND: Angong Niuhuang Wan (AGNHW, ), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated.
OBJECTIVE: This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW\'s multifaceted immunomodulation effects in-depth, emphasizing previously underexplored areas.
RESULTS: AGNHW mitigated monocyte-derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW-treated group attenuated their expressions, indicating AGNHW\'s potential to temper the post-ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post-stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries.
CONCLUSIONS: This study offers a comprehensive portrait of AGNHW\'s immunomodulation effects on ischemic stroke, illuminating its dual sites of action-both cerebral and systemic-and its nuanced modulation of cellular and molecular dynamics.