Study On The Relationship Between The Signal Chains Related To Damage And Repair Function And The Role Of CD38 In Neuro - Immunoregulatory Function - Related Signal Chain In Restrained Stress Model Rats

Objective:Explore the functions of restraint stress and CD38in neuroimmunoregulation injury and injury related repairing together with the relationships with signals of peripheral serum through analyzing changes of signal pathway associated with neuroimmunoregulation injury and repair in hippocampus, LH andAA.Methods:This research work included two parts:1、SD rats were used to manufacture acute and chronic restraint stress models while normal controls were untreated.Immunohistochemistry was used to test expression levels of IL-1β, IL-6and TGF-β1at each group in hippocampus. IL-1β, IL-6, TGF-β1and CRP expression in periphery serum were tested by ELISA. qRT-PCR was used to test expression levels of IL-1β,IL-6and TGF-β1mRNA expresion in hippocampus.2、Wild type mice and CD38knockout mice were randomly divided into immune0,2,4,6,8days’ groups. To analyze the influence of CD38deficiency on neuroimmunoregulation function, IL-1β and IL-6expression in periphery serum were tested by ELISA.Immunohistochemistry was used to test expression levels of IL-1β and IL-6at every different immune time point in LH and AA,which are neuroimmunoregulation related cerebral regions.Results:1、Compared with the normal control group, CRP expression level of chronic restraint stress group in peripheral serum is higher with statistical significance (p<0.05),while IL-1β and IL-6are higher,and TGF-β1are lower without statistical significance(p>0.05). IL-1β,IL-6and TGF-β1expression levels of acute restraint stress group are lower,and CRP is higher without statistical significance(p>0.05);Compared with chronic restraint stress group, CRP expression level of acute restraint stress group is lower with statistical significance (p<0.05), while IL-1β and IL-6are lower,and TGF-β1is higer without statistical significance(p>0.05).2、Compared with the normal control group, IL-1β,IL-6and TGF-β1expression levels of chronic restraint stress group and acute restraint stress group in hippocampus CA3are higher with statistical significance (p<0.05);Compared with chronic restraint stress group, IL-6expression level of acute restraint stress group is lower with statistical significance (p<0.05), while IL-1β and TGF-β1are lower without statistical significance(p>0.05).3、Compared with the normal control group, IL-1β mRNA expression level of chronic restraint stress group is higher with statistical significance (p<0.05) while IL-6and TGF-β1mRNA are higher without statistical significance(p>0.05),and IL-1β, IL-6and TGF-β1mRNA of acute restraint stress group in hippocampus are higher without statistical significance(p>0.05); IL-1βmRNA expression of chronic restraint stress group is higer than acute restraint stress group with statistical significance (p<0.05). There are no statistical significance(p>0.05)in IL-1β, IL-6and TGF-β1mRNA expression levels between acute restraint stress group and chronic restraint stress group.4、In immune0,2,4,6,8days’ groups, IL-1β expression in LH and AA of CD38knockout mice are higher than that of wild type mice with statistical significance (P<0.05). IL-6expression in LH and AA between CD38knockout mice and wild type mice show no significant difference(P>0.05); In immune0,2,4,6,8days’groups, IL-1β and IL-6expression in peripheral serum between CD38knockout mice and wild type mice show no significant difference (P>0.05).Conclusions:1、Acute and chronic restraint stress can result in injury of CNS,and then initiate repairing process,in which injury and repairing always coexsist. IL-1β, IL-6and TGF-β1expression levels are upregulated in hippocampus.So are the mRNA expression levels of them; Acute and chronic restraint stress have different effects on signal molecular’s expression pattern associated with stress and injury in peripheral serum. In acute restraint stress, expression levels of IL-1β,IL-6,TGF-β1and CRP have no significant change while in chronic restraint stress, IL-1β,IL-6and CRP expression continue to increase,and TGF-β1which participates in repairing decreases.2、Blocking CD38can increase IL-1β expression in neuroimmunomodulation related brain regions and peripheral serum,but have little effect on IL-6signal system.This suggests that CD38can negatively regulate IL-1β signal pathway in LH and AA.