| Objective:The purpose of this study was to investigate the neuroprotective role and mechanism of emodin on mice with sepsis.Methods:Male BALB/c mice were divided into four groups randomly: normal control group,lipopolysaccharide(LPS)group,emodin group and emodin+LPS group.Mice in emodin group and emodin+LPS group were intraperitoneally injected with emodin(20mg/kg)30min before modeling,and in the other two groups were intraperitoneally injected with same volume solvent.Then the mice in LPS group and emodin+LPS group were stimulated with LPS(15mg/kg),and in the other two groups,meanwhile,intraperitoneally injected with the same volume of normal saline.Mice were killed by cervical dislocation 18 h after LPS injection,and brain tissues and plasma samples were collected.Hematoxylin-eosin staining was performed to observe the pathological damages of brain tissues of mice;the expression of S100-? protein in plasma was measured by ELISA to evaluate the degree of brain injury;the production of lactic acid(LA)inbrain tissue was detected by colorimetric quantitative method to evaluate the degree of metabolic disorder in brain tissue;the levels of interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-?)in plasma were measured by ELISA to evaluate the degree of systemic inflammatory response;the activity of neuro-specific enolase(NSE)was measured by ELISA to evaluate the degree of neuroinflammation;the activity of acetylcholinesterase(Ach-E)in brain tissue was measured by colorimetric quantitative method to evaluate the level of acetylcholine(Ach)in brain tissue.Results:(1)Compared with the normal control group,no obvious pathological damage of brain tissues was observed in the emodin group,but obvious pathomorphological brain injury was observed in LPS group;While compared with LPS group,a significantly lighter degree of brain injury was found in emodin+LPS group.(2)The levels of Ach-E and LA in brain tissue in LPS group [(1.09±0.10)U/mg and(0.35±0.03)mmol/g,respectively]were markedly increased in comparison with those in normal control group[(0.84±0.09)U/mg and(0.16±0.03)mmol/g,respectively,P<0.05];No statistically significant differences were observed in these indexes between the emodin group and the normal control group(P>0.05).(3)The plasma levels of S100?,IL-6,TNF-? and NSE in LPS group [(0.52±0.06)ng/ml,(4207.23±90.76)pg/ml,(355.62±6.88)pg/ml and(9.02±0.78)ng/ml,respectively] were also significantly higher than those in normal control group [(0.38±0.05)ng/ml,(501.60±74.18)pg/ml,(157.41±10.65)pg/ml and(5.41±0.89)ng/ml,respectively,P<0.05];No statistically significant differences were observed in these indexes between the emodin group and the normal control group(P>0.05).(4)Compared with LPS group,the plasma levels of S100? [(0.44±0.06)ng/ml],IL-6 [(1479.50±50.53)pg/ml],TNF-? [(213.48±9.19)pg/ml] and NSE [(6.74±1.12)ng/ml] in emodin+LPS group were significantly reduced(P<0.05),and compared with LPS group,the levels in brain tissue of LA [(0.25±0.03)mmol/g protein] and Ach-E[(0.87±0.07)U/mg protein] were also markedly down-regulated in emodin+LPS group(P<0.05).Conclusions:Emodin could have a neuroprotective effect on LPS-induced acute brain injury in mice,the mechanism of which is possibly inhibition of inflammatory response and activation of cholinergic anti-inflammatory pathway. |
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