The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury  

作　　者：Yijing Zhao Tong Li Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang 

机构地区：[1]Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [2]Department of Neurosurgery,Qingdao Municipal Hospital,Qingdao,Shandong Province,China [3]Department of Medical Psychology and Ethics,School of Basic Medicine Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [4]Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China,Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University,Jinan,Shandong Province,China

出　　处：《Neural Regeneration Research》2024年第5期1084-1091,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).

摘　　要：We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关 键 词：chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-CYSTEINE lipopolysaccharide microglia miR-9-5p neuroprotection 

分 类 号：R741[医药卫生—神经病学与精神病学]