Dong Xiaohua, Jiang Dongya, Chen Shuhan, Tan Ji, Zhao Jing, Liu Xingdan, Lu Ziyi, Yeung Kelvin W K, Liao Yun, Liu Xuanyong, Ouyang Liping
Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, China.
Hongqiao International Institute of Medicine, Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, China.
Bioact Mater. 2025 Sep 2;54:531-548. doi: 10.1016/j.bioactmat.2025.08.032. eCollection 2025 Dec.
Hypoxia-Ischemia Brain Damage (HIBD) results in a widespread neuronal damage and permanent brain tissue injury due to the severe reactive oxygen species (ROS) boost induced neuroinflammation. In this work, a K doped N-C based nanozyme was fabricated for scavenging ROS. KNC could impair ROS production and M1 polarization in microglia. Beneficial from these contents, the brain damage was mitigated in HIBD rats, which was proved by the increased regional blood flow, decreased pro-inflammatory microglia and astrocyte activation. The learning and memory capabilities were restored after applying with KNC post HIBD, which was ascribed to the diminished HI-induced dendritic spine loss in hippocampal regions. RNA-seq revealed that decreased ALOX12 expression is one of the clues of neuronal protection. KNC could combine with ALOX12 and further inhibit the lipid peroxidation. These two clues obtain KNC with superior ability of inhibition of ROS boost induced brain damage post HIBD. This nanozyme provided a potential strategies and new idea of HIBD therapy.
缺氧缺血性脑损伤（HIBD）会导致广泛的神经元损伤和永久性脑组织损伤，这是由于严重的活性氧（ROS）激增引发了神经炎症。在这项工作中，制备了一种K掺杂的N-C基纳米酶用于清除ROS。KNC可以抑制小胶质细胞中ROS的产生和M1极化。得益于这些作用，HIBD大鼠的脑损伤得到减轻，这通过局部血流量增加、促炎性小胶质细胞减少和星形胶质细胞活化降低得到证明。HIBD后应用KNC可恢复学习和记忆能力，这归因于海马区HI诱导的树突棘损失减少。RNA测序显示，ALOX12表达降低是神经元保护的线索之一。KNC可以与ALOX12结合并进一步抑制脂质过氧化。这两条线索使KNC具有优异的抑制HIBD后ROS激增诱导脑损伤的能力。这种纳米酶为HIBD治疗提供了潜在策略和新思路。
