机构:[1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, Guangdong Province, China南方医科大学珠江医院[2]Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China南方医科大学珠江医院[3]Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China[4]Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China[5]Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, China北京大学深圳医院深圳市康宁医院深圳医学信息中心香港大学深圳医院[6]Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong Province, China
Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species, which causes abnormal mitochondrial function and secondary reactive oxygen species generation. This creates a vicious cycle leading to reactive oxygen species accumulation, resulting in progression of the pathological process. Therefore, breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage. Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NADPH oxidase 4, NOX4) led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage. The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress, mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage. We found that NOX4 knockdown by adeno-associated virus (AAV-NOX4) in rats enhanced neuronal tolerance to oxidative stress, enabling them to better resist the oxidative stress caused by intracerebral hemorrhage. Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria, relieved mitochondrial damage, prevented secondary reactive oxygen species accumulation, reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats. Finally, we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4. The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis, which is similar to the effect of AAV-NOX4. This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production, and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.
基金:
This study was supported by the National Natural Science Foundation of China, No. 81671125; the Natural Science Foundation of Guangdong Province, No. 2021A1515011115; and Guangzhou Science and Technology Project, No. 202102010346 (all to YZC).
第一作者机构:[1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, Guangdong Province, China
共同第一作者:
通讯作者:
通讯机构:[1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, Guangdong Province, China[6]Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong Province, China
推荐引用方式(GB/T 7714):
Ding Bo-Yun,Xie Chang-Nan,Xie Jia-Yu,et al.Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage[J].NEURAL REGENERATION RESEARCH.2023,18(8):1734-1742.doi:10.4103/1673-5374.360249.
APA:
Ding Bo-Yun,Xie Chang-Nan,Xie Jia-Yu,Gao Zhuo-Wei,Fei Xiao-Wei...&Chen Yi-Zhao.(2023).Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage.NEURAL REGENERATION RESEARCH,18,(8)
MLA:
Ding Bo-Yun,et al."Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage".NEURAL REGENERATION RESEARCH 18..8(2023):1734-1742