机构：[1]Department of Pediatrics, the Second School of Medicine, the Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China [2]Department of Pediatrics, Taizhou Hospital of Zhejiang Province afliated to Wenzhou Medical University, Linhai, Zhejiang, China 台州恩泽医疗中心台州医院[3]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [4]Scientifc research department, the Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China [5]Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, Zhejiang, China [6]Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, China
White matter injury (WMI) is a common complication of preterm birth, potentially resulting in long-term behavioral and motor abnormalities. The objective of this study is to investigate the neuroprotective effects of glycyrrhizin (GLY) on WMI, and try to elucidate the potential mechanisms. In vivo chronic hypoxia-induced WMI mouse model and in vitro oxygen-glucose deprivation (OGD) induced WMI cell model were established, and the effects of GLY on WMI were explored through multiple assays, such as western blotting, immunofluorescence, immunohistochemistry, behavioral experiments, real-time quantitative polymerase chain reaction (RT-qPCR), transmission electron microscope (TEM), molecular docking, and bioinformatics analysis. The results showed that GLY facilitated the maturation and differentiation of oligodendrocytes and enhanced the thickness as well as density of myelin sheaths. GLY also reduced inflammatory response, improved memory, learning, and locomotor performances, and alleviated anxiety in WMI mice. The neuroprotective effects of GLY may be involved in the down-regulation of HMGB1 and its associated proteins such as TLR4 and NF-kappa B. In conclusion, GLY could mitigate chronic hypoxia-induced WMI and OGD-induced oligodendrocyte injury through its anti-inflammatory effects by inhibiting the HMGB1/TLR4 pathway, suggesting a potential therapeutic avenue for WMI.
基金：
Natural Science Foundation of Zhejiang Province (LY20H040006 and LY24H020008 and LQ21H040009) and Basic Medical and Health Technology Project of Wenzhou Science and Technology Bureau (Y20220014) and
National Natural Science Foundation of China (No. 82402013),
the Key Research and Development Program of Zhejiang Province
(2023C03018), and the Fourth Batch of Wenzhou Medical University
“Outstanding and Excellent Youth Training Project” (604090352/640).
第一作者机构：[1]Department of Pediatrics, the Second School of Medicine, the Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
通讯作者：
通讯机构：[4]Scientifc research department, the Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China [5]Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, Zhejiang, China
推荐引用方式(GB/T 7714)：
Lou Jia,Ding Bingqing,Fang Mingchu,et al.Glycyrrhizin Attenuates White Matter Injury by Inhibiting Neuroinflammation through the HMGB1/TLR4 Pathway[J].MOLECULAR NEUROBIOLOGY.2024,doi:10.1007/s12035-024-04657-9.
APA：
Lou, Jia,Ding, Bingqing,Fang, Mingchu,Xie, Weiwei,Wang, Xinyi...&Zhu, Jianghu.(2024).Glycyrrhizin Attenuates White Matter Injury by Inhibiting Neuroinflammation through the HMGB1/TLR4 Pathway.MOLECULAR NEUROBIOLOGY,,
MLA：
Lou, Jia,et al."Glycyrrhizin Attenuates White Matter Injury by Inhibiting Neuroinflammation through the HMGB1/TLR4 Pathway".MOLECULAR NEUROBIOLOGY .(2024)
