Impact of vorinostat on neurological damage in mice with intracerebral hemorrhage by regulating recombinant high mobility histone B1/Toll-like receptor 4 signaling pathway
10.3969/j.issn.1004-1648.2024.04.016
- VernacularTitle:伏立诺他调节高迁移率族蛋白B1/Toll样受体4信号通路对脑出血小鼠神经功能损伤的影响
- Author:
Yangyang LI
1
;
Jian FANG
;
Xiaoxue WANG
Author Information
1. 475001 开封,河南大学第一附属医院老年神经内科
- Keywords:
high mobility group protein B1/Toll-like receptor 4 signaling pathway;
vorinostat;
intracerebral hemorrhage;
neurological impairment
- From:
Journal of Clinical Neurology
2024;37(4):292-296
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of vorinostat(SAHA)on neurological damage in mice with intracerebral hemorrhage(ICH)by regulating the high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods The ICH mouse model was established by injecting typeⅦcollagenase.The model mice were randomly grouped into ICH group,SAHA group(15 mg/kg SAHA),recombinant high mobility histone B1(rHMGB1)group(16 μg/kg rHMGB1)and SAHA+rHMGB1 group(16 μg/kg rHMGB1+15 mg/kg SAHA),with 10 mice in each group.Ten mice without injection of type Ⅶ collagenase were used as the sham operation group.After the intervention,the neurological deficit score(NDS)was performed on the mice.The cognitive impairment and brain edema changes,serum TNF-α and IL-1β levels,the number of neuronal apoptosis,and the expression of HMGB1/TLR4 pathway-related proteins in tissues surrounding the hematoma were detected.Results Compared with those in ICH group,NDS score,cerebral edema rate,the number of neuronal apoptosis,TNF-α level,IL-1β level and HMGB1 and TLR4 protein expression in sham operation group and SAHA group were significantly decreased,and the resolution index was significantly increased(all P<0.05);NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-α level,IL-1β level and HMGB1 and TLR4 protein expression in rHMGB1 group were significantly increased,and resolution index was significantly decreased(all P<0.05).Compared with those in SAHA+rHMGB1 group,NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-α level,IL-1β level and HMGB1 and TLR4 protein expression in SAHA group were significantly decreased,and resolution index was significantly increased(all P<0.05);NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-α level,IL-1β level and HMGB1 and TLR4 protein expression in rHMGB1 group were significantly increased,and resolution index was significantly decreased(all P<0.05).Conclusion SAHA inhibits the inflammatory response of HMGB1/TLR4 signaling pathway and improves neural function in ICH mice.