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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

查看全文 作　　者：Fudong [1,2]Li;Xiaofei [2]Sun;Kaiqiang [3]Sun;Fanqi [2]Kong;Xin [4]Jiang;Qingjie [1]Kong 高影响力作者 机构地区：[1]Department of Orthopedics,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China;[2]Department of Orthopedic Surgery,Spine Center,Shanghai Changzheng Hospital,Naval Medical University,Shanghai,China;[3]Department of Orthopedic Surgery,Naval Medical Center,Naval Medical University,Shanghai,China;[4]Department of Anesthesiology,Shanghai Changzheng Hospital,Naval Medical University,Shanghai,China高影响力机构 出　　处：《Neural Regeneration Research》索引2024年第19卷第8期,共10页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China,Nos.81801226(to QK and XS)and 82101445(to XJ)。 摘　　要：Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes. 关 键 词：INFLAMMASOME inflammation lupenone MICROGLIA polarization PYROPTOSIS spinal cord injury
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