神经病理性疼痛致抑郁大鼠海马促炎细胞因子含量的变化

Changes of hippocampal levels of pro-inflammatory cytokines in rats with depression induced by neuropathic pain

目的观察神经病理性疼痛致抑郁大鼠海马促炎细胞因子含量的变化,并探讨其与抑郁严重程度的关系。方法成年雄性SD大鼠28只,随机分为两组:假手术组(Sham组)和保留性坐骨神经损伤组(SNI组),每组14只。于术前1d及术后7、14、21d测试机械痛阈值(MWT);于术前1~3d测试糖水偏好、强迫游泳实验基础值;术后21~23d进行糖水偏好实验、强迫游泳实验;行为学测试结束后取海马组织,采用ELISA法检测海马中IL-1β、IL-6、TNF-α的含量,并对其与糖水偏好的相关性进行分析。结果与Sham组比较,SNI组大鼠在术后7、14、21d MWT明显降低(P<0.001),术后21d糖水偏好明显降低(P<0.01),术后23d强迫游泳不动时间明显延长(P<0.05);术后21d海马组织IL-6、TNF-α含量明显升高(P<0.05或P<0.01),而IL-1β含量差异无统计学意义;SNI组海马组织IL-1β(r2=0.60,P<0.01)、IL-6(r2=0.55,P<0.01)、TNF-α(r2=0.60,P<0.01)含量与糖水偏好呈明显负相关。结论神经病理性疼痛致抑郁大鼠海马促炎细胞因子IL-6、TNF-α含量升高,且与抑郁严重程度呈负相关。

Objective To observe changes of hippocampal levels of pro-inflammatory cytokines in rats with neuropathic pain-induced depression,and to explore the relationship between hippocampal levels of pro-inflammatory cytokines and severity of depression.Methods Twenty-eight adult male rats were randomly divided into two groups：group sham（n=14）and spared nerve injury（group SNI）（n=14）.Mechanical withdrawal thresholds（MWT）were measured 1day before and 7,14and21 days after operation.Sucrose preference test and forced swim test were tested 1-3days before and21-23 days after operation.After test,hippocampus was collected.The hippocampal levels of interleukin（IL）-1β,IL-6and tumor necrosis factor-α（TNF-α）were measured by ELISA.Correlational relationships between hippocampal levels of pro-inflammatory cytokines and sucrose preference were evaluated.Results Compared with group sham,MWT was decreased 7,14,21 days after operation（P〈0.001）.Group SNI displayed decreased sucrose preference 21 days after operation（P〈0.01）and increased immobility time in FST 23 days after operation（P〈0.05）.The levels of IL-6and TNF-αwere increased in hippocampus（P〈0.05 or P〈0.01）.No significant difference was observed in IL-1β.The hippocampal levels of IL-1β（r2=0.60,P〈0.01）,IL-6（r2=0.55,P〈0.01）and TNF-α（r2=0.60,P〈0.01）were negatively correlated with sucrose preference.Conclusion The hippocampal levels of pro-inflammatory cytokines IL-6and TNF-αare increased in rats with depression induced by neuropathic pain,and the levels of hippocampal pro-inflammatory cytokines are negatively correlated with the severity of depression.