Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation  

作　　者：Xin QUAN Teng MA Kai GUO Huan WANG Cai-yong YU Chu-chu QI Bao-qiang SONG 

机构地区：[1]Department of Plastic Surgery,Xijing Hospital,the Fourth Military Medical University,Xi'an 710032,China [2]Department of Orthopedics,Xijing Hospital,the Fourth Military Medical University,Xi'an 710032,China [3]Department of Burns and Cutaneous Surgery,Xijing Hospital,the Fourth Military Medical University,Xi'an 710032,China [4]Department of Respiratory Medicine,Xi'an Hospital of Traditional Medicine,Xi'an 710000,China [5]Department of Neurobiology,School of Basic Medicine,the Fourth Military Medical University,Xi'an 710032,China

出　　处：《Current Medical Science》2023年第4期749-758,共10页当代医学科学（英文）

基　　金：supported by the National Natural Science Foundation of China Young Scientists Fund(No.81801216,No.81802143,No.81901966);the China Postdoctoral Foundation(No.2018M633748).

摘　　要：Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.

关 键 词：spinal cord injury proinflammation oxidative stress MACROPHAGE acrolein scavenger 

分 类 号：R651.2[医药卫生—外科学]