Activation Of The Cholinergic Anti-inflammatory Pathway By Nicotine Ameliorates Lipopolysaccharide-induced Inflammatory Reaction In The Splenic Tissues Of Septic Mice

Objective:The aim of this study was to explore the protective effect of nicotine on spleen injury induced by lipopolysaccharide in mice with sepsis,and to determine its molecular mechanism.Methods:Sixty male BALB/c Mice were randomly divided into five groups(n=12 per group):control,LPS,Nicotine+LPS,MLA+Nicotine+LPS,MLA+ LPS.Mice in the LPS group were injected with LPS(10 mg/kg)to produce a mouse model of sepsis.Nicotine+LPS group received intraperitoneal injection of nicotine 60 minutes before the intraperitoneal injection of LPS in mice,at a dose of 1.2 mg/kg.In the MLA+Nicotine+LPS group,MLA was injected intraperitoneally before the intraperitoneal injection of LPS and nicotine in mice at a dose of 2.4 mg/kg.In the MLA+LPS group,only MLA 2.4 mg/kg was injected 30 minutes before the intraperitoneal injection of LPS in mice.In the Control group,only saline was injected intraperitoneally.Two hours after the observation,the mice were given an overdose of phenobarbital and sacrificed.Results:Compared with the Control group,the levels of TNF-? and IL-6 in serum in the LPS group were significantly increased,and the protein levels and mRNA levels of TNF-? and IL-6 in the spleen tissues were elevated.The level of NF-?B p65,p-I?B/I?B also increased,and the difference was statistically significant(p<0.05).Compared with LPS group,the expression of TNF-?and IL-6 in serum and tissues of Nicotine+LPS group was significantly decreased,and the levels of NF-?B p65 and p-I?B/I?B in tissues were also significantly decreased.The difference was statistically significant(p<0.05).Compared with Nicotine+LPS group,the expression of TNF-? and IL-6 in serum and tissues of MLA+Nicotine+LPS group was significantly increased,and the levels of NF-?B p65 and p-I?B/I?B in tissues were also significantly increased.The difference was statistically significant(p<0.05).Conclusions:The results suggest that nicotine has a protective effect on spleen inflammation caused by LPS-induced sepsis.This protective effect may be achieved by activating the cholinergic anti-inflammatory pathway,which in turn inhibits the NF-?B inflammatory pathway,reduces the level of inflammatory cytokines and reduces the systemic inflammatory response.