丰富环境对坐骨神经慢性压迫小鼠痛阈及抑郁样行为的影响

Effect of enriched environment on the pain threshold and depressive behavior in mice with chronic constriction injury

目的观察丰富环境(EE)对坐骨神经慢性压迫(CCI)小鼠痛阈及抑郁样行为的影响及可能机制。方法 C57/BL6小鼠随机分为5组(n=12):假手术组(Sham组)、CCI+标准环境(SE)组(CS组)、CCI+EE组(CE组)、CCI+EE+替莫唑胺(TMZ,抑制神经细胞再生的药物)组(CET组),CCI+EE+脂多糖(LPS)组(CEL组),于术后分别行机械刺激阈值(PWT)、热刺激潜伏期(PWL)、强迫游泳检测,计算糖水偏好,同时行海马Brdu、ki67、DCX阳性细胞及TNF-α、IL-1β检测。结果与Sham组比较,CS组术后3、7、14、28、35和42d时PWT明显降低,PWL明显缩短,术后35d强迫游泳不动时间明显延长,术后45d糖水偏好明显降低(P<0.05);与CE组比较,CS、CEL组术后35d和42dPWT明显降低,PWL明显缩短,(P<0.05);CS、CET和CEL组术后35d强迫游泳不动时间明显延长,术后45d糖水偏好明显降低(P<0.05)。与Sham组比较,术后42d,CS组Brdu、ki67、DCX阳性细胞明显减少,TNF-α、IL-1β水平明显增加(P<0.05);与CE组相比,术后42d,CS和CEL组Brdu、ki67、DCX阳性细胞明显减少,TNF-α、IL-1β水平明显增加(P<0.05)。结论 EE可改善CCI小鼠痛阈、抑郁样行为及神经再生障碍;抑制神经再生可阻断EE对CCI小鼠抑郁样行为的改善,但不影响其痛阈;增强中枢炎症反应可减弱EE对CCI小鼠痛阈及抑郁样行为的改善。

Objective To observe the effect of enriched environment（EE）on the pain threshold and depression-like behavior in mice with chronic constriction injury（CCI）and the underlying mechanism.Methods Sixty C57/BL6 mice were equally randomized into five groups：sham operation group（group Sham）,CCI＋standard environment（SE）group（group CS）,CCI＋EE group（group CE）,CCI＋EE＋temozolomide group（group CET）,CCI＋EE＋lipopolysaccharide group（group CEL）.The paw withdraw threshold（PWT）,paw withdraw latency,forced swim test（FST）and sucrose preference test（SPT）were evaluated,after the operation,meanwhile the hippocampal bromodeoxyuridine（Brdu）,ki67 and doublecortin（DCX）positive cells,tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）were determined.Results Compared with group Sham,the PWT,PWL,sucrose consumption and Brdu,Ki67,DCX positive cells were significantly decreased,the immobility time and levels of TNF-αand IL-1βwere obviously increased in group CS（P0.05）.Compared with group CE,the PWT,PWL,sucrose consumption and Brdu,Ki67,DCX positive cells were significantly decreased in groups CS and CEL.The immobility time was obviously increased in groups CS,CET and CEL,moreover,the levels of TNF-αand IL-1βwere significantly increased in groups CS and CEL（P0.05）.Conclusion EE can improve the neuropathic pain,depression-like behavior and neural regeneration in mice with CCI.The inhibition of neural regeneration can block EEinduced improvement of depression-like behavior,but does not affect the pain threshold in mice with CCI.The augmentation of central inflammation can attenuate EE-induced improvement of pain threshold and depression-like behavior in mice with CCI.