Retinoic Acid Ameliorates Brain Hippocampal Inflammation And Oxidative Stress Induced By Lipopolysaccharide Through The NF-κB/NLRP3 Pathways

Objective To study the protective effect of retinoic acid on lipopolysaccharide induced hippocampal inflammation and oxidative stress in mice and its possible mechanism.Methods40 male healthy BALB / c mice were randomly assigned to 4 groups,10 in each group: control group,LPS(10 mg · kg-1,i.p.)model group,LPS + RA(3mg · kg-1 · D-1,i.g.)group and LPS + RA(15 mg · kg-1 · D-1,i.g.)group.After14 days of administration of retinoic acid in advance,LPS(10 mg · kg-1)was injected into the abdominal cavity of all groups except the control group.After 8hours,the hippocampus and serum were taken and placed in-86℃refrigerator.Interleukin-1β(IL-1β)and Interleukin-18(IL-18)in serum and hippocampus were tested by ELISA method.Immunohistochemistry method was used to detected the expression and distribution of Nuclear Factor-κB(NF-κB)in the hippocampus.The expression of Toll-like receptor 4(TLR-4)、NF-κB、caspase-1、NLR family protein containing a pyrin domain 3(NLRP3)、Apoptosis-associated speck-like protein containing a caspase activation and recruitment domain,CARD(ASC)、 IL-1β and IL-18 were determined by Western Blotting.The level of reactive oxygen species(ROS)was measured by using dihydroethidium(DHE)staining.ELISA kits for superoxide dismutase(SOD)and malondialdehyde(MDA)were used to examine the SOD and MDA content in serum.Results Compared with control group,LPS administration resulted in(1)the nuclear structure in some of the hippocampal neurons was unclear,with nuclear pyknosis,nuclear dissolution and nuclear fragmentation.(2)increased levels of IL-18 and IL-1β in the mouse blood serum and hippocampus.(3)increased the expression of NF-κB and TLR-4 、 NF-κB(in nucleus)、caspase-1、NLRP3、ASC、IL-1β and IL-18 in mouse hippocampus.(4)the expression of ROS increased in the mouse hippocampus.(5)decreased the expression of SOD and increased the expression of MDA in the mouse blood serum and hippocampus.Compared with LPS group,RA administration resulted in(1)the nuclear structure in some of the hippocampal neurons was clear,and the phenomenon of nuclear pyknosis,nuclear dissolution and nuclear fragmentation were evidently alleviated.(2)decreased levels of IL-18 and IL-1β in the mouse blood serum and hippocampus.(3)decreased the expression of NF-κB and TLR-4、NF-κB(in nucleus)、caspase-1、NLRP3、ASC、IL-1β and IL-18 in mouse hippocampus.(4)the expression of ROS decreased in the mouse hippocampus.(5)increased the expression of SOD and decreased the expression of MDA in the mouse blood serum and hippocampus.Compared with the low dose group,the improvement effect of tne high dose group was more obvious.Conclusions RA has protective effects on LPS induced hippocampal inflmmation and oxidative stress,which might be mediated by NF-κB/NLRP3 signaling pathway.These findings provide a theoretical basis for further study of the protective effect of RA on inflammation and oxidative stress in hippocampus.