Roles of Keap1-Nrf2 and NF-κB signaling pathways in lipopolysaccharide-induced brain injury
10.7644/j.issn.1674-9960.2024.07.001
- VernacularTitle:Keap1-Nrf2和NF-κB信号通路介导脂多糖诱导的脑损伤效应研究
- Author:
Yichen LIU
1
,
2
;
Dongfei YAN
;
Zhixin LI
;
Yingchun MAO
;
Zhihui LI
;
Guofu DONG
;
Changzhen WANG
Author Information
1. 军事科学院军事医学研究院,北京 10085
2. 联勤保障部队第九九○医院儿科,河南驻马店 463000
- Keywords:
sepsis;
sepsis-associated encephalopathy;
lipopolysaccharide;
Keap1;
NF-κB;
Nrf2
- From:
Military Medical Sciences
2024;48(7):481-486
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of Kelch-like-epichlorohydrin-associated protein 1/nuclear factor erythroid-derived factor-2-related factor 2(Keap1-Nrf2)and nuclear factor-κB(NF-κB)signaling pathways in sepsis-associated encephalopathy(SAE).Methods Male C57BL/6J mice of SPF were randomly divided into four groups(n=10):the control group and LPS 6 h,24 h and 48 h groups.The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT).ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum,and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice.Real-time quantitative PCR(qPCR)was adopted to detect the mRNA levels of toll-like receptor4(Tlr4),NF-κB,Keap1 and Nrf2 in the hippocampus,and to determine protein expressions of NF-κB a Nrf2、Keap1 and Tlr4 with Western blotting.Results Compared to the control group,the serum concentrations of interleukin 6(IL-6)in lipopolysaccharide(LPS)groups increased at 6 h,and reached the peak at 24 h and 48 h(P＜0.01).The levels of serum interleukin 18(IL-18)in the LPS groups increased significantly at 6 h and 24 h(P＜0.01)but there was no statistically significant difference compared with the 48h group.The results indicated the activity of superoxide dismutase(SOD)and glutathione(GSH)in brain tissues in LPS groups increased(P＜0.01).OFT results showed the time spent in the center of the open field,the distance covered around the center,and total distance covered by mice in LPS groups were significantly reduced(P＜0.01),except for the time spent in the center of the open field in the LPS 24 h group.The mRNA expressions of Tlr4 and(LPS 6 h,48 h)NF-κB in the hippocampus tissue of mice in LPS groups were elevated(P＜0.05),so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group.Additionally,the protein expressions of NF-κB,Keap1 and Tlr4 increased in LPS groups,so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P＜0.05).Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.
