Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, People's Republic of China.
Department of Neurology, Affiliated Hospital, Yangzhou University, Yangzhou 225001, PR China.
ACS Biomater Sci Eng. 2021 Jan 11;7(1):299-310. doi: 10.1021/acsbiomaterials.0c01312. Epub 2020 Dec 21.
Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood-brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (FeO) nanoparticles with intrinsic enzyme-like activities. We find that FeO nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified FeO nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. analysis shows that PEG-modified FeO nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood-brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified FeO nanozymes can facilitate blood-brain-barrier reconstruction and protect neurons following ischemic stroke.
脑缺血性中风会刺激过量的活性氧(ROS),从而导致血脑屏障破坏、神经元死亡和脑梗死加重。因此,开发一种抗氧化策略来治疗中风至关重要。在此,我们报告了一种使用具有内在酶样活性的氧化铁(FeO)纳米粒子促进中风治疗的饮食策略。我们发现 FeO 纳米酶具有过氧化物酶、过氧化氢酶和超氧化物歧化酶的三重酶样活性,因此可能具有调节 ROS 水平的能力。重要的是,胃内给予聚乙二醇(PEG)修饰的 FeO 纳米酶可显著降低脑缺血性中风后啮齿动物模型的脑梗死和神经元死亡。分析表明,PEG 修饰的 FeO 纳米酶定位于脑血管中,通过降低丙二醛和增加 Cu/Zn SOD 来改善局部氧化还原状态,并通过提高海马体中的 ZO-1 和 Claudin-5 来促进血脑屏障的恢复。总之,我们的结果表明,饮食中的 PEG 修饰的 FeO 纳米酶可以促进血脑屏障的重建,并在缺血性中风后保护神经元。