机构：[1]Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, China[2]Research Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China[3]Wenling Maternal and Child Health Care Hospital, Wenling City, China[4]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hypoxic-ischemic brain damage (HIBD) arises from perinatal hypoxia, a leading cause of neonatal mortality during the perinatal period, as well as subsequent disabilities beyond the neonatal stage. While there is currently no unified and comprehensive treatment approach for hypoxic-ischemic encephalopathy (HIE), hypothermia therapy represents the only recognized clinical intervention. Nevertheless, the efficacy of hypothermia therapy remains limited. Recently, atomically precise metal nanoclusters (NCs), an emerging class of nanomaterials, has displayed promising potential in biomedical field. This study aimed to assess whether glutathione-protected Au-22 nanoclusters (GSH-Au-22 NCs) could mitigate brain damage induced by hypoxic-ischemic (HI) injury in rats and oxygen-glucose deprivation (OGD) in cortical primary neurons while exploring the underlying protective mechanisms. In vitro findings revealed that GSH-Au-22 NCs enhanced cell activity, mitigated inflammatory reactions, and reduced oxidative stress induced by oxygen-glucose deprivation in cortical primary neurons. In vivo, GSH-Au-22 NCs significantly diminished cerebral infarction volume, alleviated inflammatory responses, reduced oxidative stress, facilitated tissue structure recovery, attenuated apoptosis resulting from HIE, and enhanced long-term learning and memory abilities following HI injury. Mechanistically, GSH-Au-22 NCs ameliorated the Sirt3/SOD2 signaling pathway, thereby exerting a protective effect against HIBD. Furthermore, the protective impact of GSH-Au-22 NCs was reversed upon knocking down SOD2. In conclusion, our findings demonstrate that GSH-Au-22 NCs modulate the Sirt3/SOD2 signaling pathway, thereby mitigating HI brain damage.
基金：
Basic Medical and Health Technology Project of Wenzhou Science and Technology Bureau [Y20220014]; Natural Science Foundation of Zhejiang Province [LY20H040006]; Zhejiang Medical and Health Science and Technology Plan Project [2022KY448]
