| ObjectiveTo observe the effects of taVNS on chronic unpredictable mild stress(CUMS)-induced depression in rats and the expressions of NLRP3,NF-?B,and IL-1? in the prefrontal cortex,so as to explore its anti-depression mechanism.Method1.Experimental groups:24 male SD rats were divided into 4 groups,control group,model group,taVNS group,and tnVNS group.Rats in each group were fed for 1 week before the experiment2.Modeling methods:In this study we established the model by the method of orphanage combined with continuous 35 days chronic unpredictable mild stress.Stimulation methods included moist bedding(24h),day-night reversal(12/12h),restraint(2h),tail pinching(3min),cold water swimming(4?,5min),fasting(24h),and water deprivation(24h).One of the means was arranged daily,and the means for two consecutive days were not repeatable,means were arranged randomly within 35 days3.Intervention methods:(1)taVNS intervention method:2%isoflurane inhalation anesthetized rats,using stimulator HANS-200A,connected with positive and negative circular self-adsorbing conductive magnets,non-invasively fixed to the bilateral ear cavity where is the ear vagus nerve distribution area.dilatational wave,intensity 2mA,frequencies of 2/15Hz,1 time/day,30 minute/time and altogether 21 days.(2)tnVNS intervention method:2%isoflurane inhalation anesthetized rats,using stimulator HANS-200A,connected with positive and negative circular self-adsorbing conductive magnets,non-invasively fixed to the edge of both ears of rats,where is no ear vagus nerve distribution,dilatational wave,intensity 2mA,frequencies of 2/15Hz,1 time/day,30 minute/time and altogether 21 days.4.Experimental methods of each group(1)Control group:6 rats were kept in a cage,no modeling or intervention(2)Model group:The rats were kept alone,and they received daily CUMS modeling for 35 days.(3)taVNS group:the rats were kept alone and received daily CUMS modeling for 35 days.On the 14 day of the experiment,taVNS was be applied to the rats 2 hours before daily modeling,once a day for 21 days.(4)tnVNS group:the rats were kept alone and received daily CUMS modeling for 35 days.On the 14 day of the experiment,tnVNS was be applied to the rats 2 hours before daily modeling,once a day for 21 days.5.Indicator detection and methods:The behavior of rats was evaluated by body weight,open-field test and sucrose preference test on day 0,14 and 35 of the experiment;The levels of NF-?B,NLRP3 and IL-1? in prefrontal cortex of rats in each group were detected by Western Blot method after the experiment.Result1.Effects on rats behavior:At the beginning of the experiment,there were no significant differences in each group(P>0.05);On the 35th day of the experiment,compared with the control group,the model group showed a significant decrease of the number of crossing and rearing,the body weight and the sugar preference index(P<0.01).Compared with the model group,the body weight,the sugar preference index,the number of crossing and rearing in the taVNS group were significantly increased(P<0.05,P<0.01);Compared with the model group,the sugar preference index,the number of crossing and rearing in the tnVNS group were significantly increased(P<0.01),but all were lower than those in the taVNS group.2.Effects on the expresson level of NLRP3,NF-?B,and IL-1? in the prefrontal cortex(1)Compared with the control group,the expression of NF-?B in the model group was significantly increased(P<0.01);Compared with the model group,the expression of NF-kappa B in the taVNS group was significantly decreased(P<0.05);There was no significant difference in the expression of NF-?B between tnVNS group and model group.(2)Compared with the normal group,the expression of NLRP3 was significantly increased in the model group(P<0.01);compared with the model group,the expression of NLRP3 was significantly decreased in the taVNS group(P<0.01);compared with the model group,the expression of NLRP3 was significantly decreased in the tnVNS group(P<0.05).(3)Compared with the normal group,the expression of IL-1 ? in the model group was significantly increased(P<0.01);Compared with the model group,the expression of IL-1 ?in the taVNS group and the tnVNS group was significantly decreased(P<0.01),and the taVNS group decreased more.Conclusion1.Both taVNS and tnVNS could improve the behavioral of rats,but the effect of taVNS was stronger than that of tnVNS in all aspects.Separated living method combined with CUMS resulted in significantly increased expression of NF-? B,NLRP3,IL-1 ? in the prefrontal cortex of model rats,which could be reversed by taVNS intervention.2.The mechanism by which VNS improves depressive behavior in rats may be related to the reduction of NF-? B level and NLRP3 inflammasome activation,which in turn reduces IL-1? secretion,thereby alleviating brain injury caused by inflammatory response. |
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