Linarin inhibits microglia activation-mediated neuroinflammation and neuronal apoptosis in mouse spinal cord injury by inhibiting the TLR4/NF-κB pathway
10.12122/j.issn.1673-4254.2024.08.18
- VernacularTitle:蒙花苷通过抑制TLR4/NF-κB通路抑制小鼠脊髓损伤后小胶质细胞活化介导的神经炎症和神经元凋亡
- Author:
Linyu XIAO
1
;
Ting DUAN
;
Yongsheng XIA
;
Yue CHEN
;
Yang SUN
;
Yibo XU
;
Lei XU
;
Xingzhou YAN
;
Jianguo HU
Author Information
1. 蚌埠医科大学第一附属医院康复科,安徽 蚌埠 233004
- Keywords:
spinal cord injury;
neuroinflammation;
apoptosis;
TLR4/NF-κB linarin
- From:
Journal of Southern Medical University
2024;44(8):1589-1598
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.
