Effect Of Nimesulide On CUMS-induced Depressive Behavior In Rats

bjective: Chronic unpredicted mild stress was taken to establish rat depression model. To investigate the effect of nimesulide on the depressive-like behaviors caused by chronic mild unpredictable mild stress(CUMS) in rats. Methods:(1)120Male SD rats were randomly divided into following groups: normal control group、CUMS group、Fluoxetine (3mg/kg.d) and nimesulide (3,6and12mg/kg.d).except normal control group, Rats were subjected to the following kinds of stressors(one stressors one day):24h period of food deprivation,24h period of food deprivation, the tail clamps for1min,5min period of swimming in clod water(5℃), damp bedding, turning night into day,5min period of swimming in hot water(45℃),24h period of45°cage tilt, taint stimulated. Each stressor was repeated2or3times during the21-day stress procedure to establish rat depression model. Fluoxetine (3mg/kg.d) and nimesulide (3,6and12mg/kg.d) was administrated after stress procedure for21days.(2) The open-field test, elevated plus-maze (EPM) assay and forcedswimming test were used to evaluate the depression behaviors of rats.HE stainting was used to observe hippocampal pathological changes. SYN、NGF、BDNF、5-HT1Aprotein expression expression was detected by immunohistochemistry. IL-1β,IL-6,TNF-α,IL-4,IL-10levelswere detected by method of ELISA.(3)Screening of the nosogenesis of depression carried out using ITRAQ.RESULTS:(1)chronic mild unpredictable stress (CUMS) rats causeda decrease of the crossing and rearing movement times from open-field test. a significant increase of immobility time from forced swimming test, and a significant decrease of the proportion of times entering the open arm、the proportion of time into the open arm andthe total times of entering the open arm and closed arm. The levels of IL-1β,IL-6and TNF-α of rats increased,the level of IL-4、IL-10of rats decreased.CUMS significantly decreased the expression ofSYN、NGF、BDNF、5-HT1Areceptor protein in rat hippocampi.(2)nimesulide remarkably improve depressive behavior, The changeof IL-1β,IL-6and TNF-α concentrations was significantly blunted inCUMS rats by nimesulide. The change of IL-4, IL-10concentrations was increased in CUMS rats by nimeisulide. nimesulide significantly increased the expression of SYN、NGF、BDNF、5-HT1Aprotein in CUMS rats with dose-dependent manner.(3) As compared with that of the normal control group,54differentially expressed proteins were identified from CUMS group,41proteins increased and13proteins downregulation.75differentially expr essed proteins were identified from nimeisulide of3mg/kg group byITRAQ,55proteins increased and20proteins downregulation.40differentially expressed proteins were identified from nimeisulide of6mg/kg group by ITRAQ,31proteins increased and9proteins downregulation.42differentially expressed proteins were identified fromnimeisulide of12mg/kg group by ITRAQ,12proteins increased and30proteins downregulation.70differentially expressed proteins were identified from nimeisulide of Fluoxetine group by ITRAQ,57proteins increased and13proteins downregulation.Conclusion: The chronic mild stressed depression rats were established by chronic unpredictable mild stress and separation after21days. Nimesulide have a potential therapeutic benefit against CUMS-induced depression and anti-inflammation、protection of neural plasticity may be involved in its protective mechanism. ITRAQ based screening is useful in discovering the nosogenesis of depression relatedproteins.