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Baicalin-loaded macrophage-derived exosomes ameliorate ischemic brain injury via the antioxidative pathway

机译:加载的巨噬细胞衍生的外泌体通过抗氧化途径改善缺血性脑损伤

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摘要

Baicalin (BA), a strong free radical scavenger, has been demonstrated to exert neuroprotective effects in the treatment of ischemic stroke. However, its clinical application has been limited due to its inability to target the brain and its poor solubility. In this study, we designed novel brain-targeted BA-loaded macrophage-derived exosomes (Exo-BA) to induce neuroprotection against ischemic stroke in animal models. The results revealed that with the help of Exo, the solubility of BA was significantly enhanced. In addition, Exo-BA displayed better brain targeting ability than free BA, as they induced the transfer of more BA into the brain, in a transient middle cerebral artery occlusion/reperfusion (tMCAO) model and permanent middle cerebral artery occlusion (pMCAO) model. Compared with free BA, Exo-BA significantly reduced the generation of reactive oxygen species (ROS) and activated the Nrf2/HO-1 pathway in neurons, thus significantly alleviating cerebral ischemic injury in a stroke model.
机译:Baicalin(Ba)是一种强烈的自由基清除剂,已经证明在缺血性卒中治疗中发挥神经保护作用。然而,由于无法靶向大脑及其不良溶解度,其临床应用受到限制。在这项研究中,我们设计了新型的脑靶向BA负载的巨噬细胞衍生的外泌体(EXO-BA),以诱导动物模型中缺血中风的神经保护脑。结果表明,在EXO的帮助下,BA的溶解度明显增强。此外,EXO-BA显示比免费的BA更好的脑靶向能力,因为它们诱导更多BA进入大脑,在瞬时中脑动脉闭塞/再灌注(TMCAO)模型和永久性中动脉闭塞(PMCAO)模型中。与游离BA相比,EXO-BA显着降低了活性氧物质(ROS)的产生,并在神经元中激活NRF2 / HO-1途径,从而显着减轻行程模型中的脑缺血性损伤。

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