Effect of remimazolam on LPS-induced microglial M1 polarization by regulating TLR4
10.3969/j.issn.1009-0126.2025.01.022
- VernacularTitle:瑞马唑仑通过调节Toll样受体4对脂多糖诱导的小胶质细胞M1型极化的影响
- Author:
Feng JIANG
1
;
Jin LI
;
Wenjie LIU
;
Gaofeng ZHANG
;
Yang YUAN
;
Fei SHI
Author Information
1. 266033 青岛大学附属青岛市海慈医院(青岛市中医医院)麻醉科
- Publication Type:Journal Article
- Keywords:
microglia;
benzodiazepines;
lipopolysaccharides;
Toll-like receptor 4
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2025;27(1):100-104
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)%vs(1.561±0.08)%]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P<0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)%vs(14.757±0.986)%]and TLR4 induced by LPS(P<0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)%vs(3.767±0.364)%,all P<0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P>0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.