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.
基金:
Science and Technology Commission of Shanghai Municipality [24CL2900700]; Fundamental Research Funds for The Central Universities [YG2023ZD29, 2232023A-10]; National Natural Science Foundation of China [32371397, U21A20100]; Research Fund of Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine [2023DHYGJC-YBA01]; Laboratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery [2024JZWC-ZDB03]; Natural Science Foundation of Shanghai [24ZR1463600]; Talent project of Shanghai Tongren Hospital [TRKYRC-xx02]
第一作者机构:[1]Shanghai Jiao Tong Univ, Tongren Hosp, Inst Med Robot, Shanghai Key Lab Flexible Med Robot, Shanghai, Peoples R China[3]Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Int Inst Med, Sch Med, 1111 XianXia Rd, Shanghai 200336, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Shanghai Jiao Tong Univ, Tongren Hosp, Inst Med Robot, Shanghai Key Lab Flexible Med Robot, Shanghai, Peoples R China[2]Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram, Shanghai 200050, Peoples R China[3]Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Int Inst Med, Sch Med, 1111 XianXia Rd, Shanghai 200336, Peoples R China[4]Donghua Univ, Coll Biol Sci & Med Engn, Shanghai 201620, Peoples R China[6]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Pharm, Shanghai 200080, Peoples R China[*1]Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University,Shanghai, China[*2]State Key Laboratory of High Performance Ceramics, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China