丰富环境对脓毒症相关性脑病小鼠认知功能的影响及NPAS4/BDNF相关机制

Effect of enriched environment on cognitive function induced by sepsis-associated encephalopathy and NPAS4/BDNF related mechanisms

目的观察丰富环境对脓毒症相关性脑病小鼠认知功能的影响,并探讨神经元PAS结构域蛋白4(NPAS4)/脑源性神经营养因子(BDNF)的相关机制。方法成年雄性C57BL/6小鼠60只随机分为三组:假手术+标准环境组(SS组,n=12)、盲肠结扎穿孔(CLP)+标准环境组(CS组,n=24)和CLP+丰富环境组(CE组,n=24)。术毕三组分别饲养在标准环境和丰富环境中29d,术后29d行条件性恐惧实验,并采用免疫印迹法、高尔基染色分别检测NPAS4、BDNF及海马树突棘密度的改变。结果与SS组比较,CS组的场景性僵直时间、树突棘密度、NPAS4、BDNF水平明显降低(P<0.05);与CS组比较,CE组场景性僵直时间、树突棘密度、NPAS4、BDNF水平明显升高(P<0.05)。三组条件性僵直时间差异无统计学意义。结论丰富环境可明显改善脓毒症相关性脑病小鼠的认知功能损伤,这可能与其上调海马NPAS4/BDNF表达,增强海马突触可塑性有关。

Objective To observe the effects of enriched environment on cognitive function in mice with sepsis-associated encephalopathy and to study the neuron PAS domain protein 4（NPAS4）/brain deprive neurotrophic factor（BDNF）related mechanisms.Methods Sixty adult male mice were divided randomly into three groups：sham operation with standard environment group（group SS,n=12）,cecal ligation and puncture with standard environment group（group CS,n=24）,cecal ligation and puncture with enriched environment group（group CE,n=24）.All mice were reared in standard environment or enriched environment for 28 days.The fear condition test was conducted on day 29 after operation in mice.The change of NPAS4 and BDNF,the density of dendritic spine were detected by western blot or golgi staining.Results Compared with group SS,the context freezing time,NPAS4 and BDNF expression and the density of dendritic spine in hippocampus decreased significantly in group CS（P 0.05）.Compared with group CS,the context freezing time,NPAS4 and BDNF expression and the density of dendritic spine in hippocampus increased significantly in group CE（P〈0.05）.No significant difference was observed in the conditional freezing time among three groups.Conclusion Enriched environment can obviously improve cognitive function impairment induced by sepsis-associated encephalopathy,which may be related with up-regulated expression of NPAS4/BDNF,and promoted synaptic plasticity.