目的 建立慢性束缚应激（CRS）和慢性不可预见性应激（CUMS）模型，观察C57BL/6小鼠行为学指标，海马区及脾脏结构及相关因子基因表达的差异，探讨不同慢性应激造模手段对小鼠神经免疫系统的影响，为抑郁症发病机制及抗抑郁药初筛选提供实验依据。 方法 建立6周的对照组、CRS及CUMS小鼠模型共45只，通过行为学评价测定小鼠行为学指标；运用HE染色观察小鼠大脑海马区及脾脏组织形态；运用尼氏染色观察海马区神经元受损情况；Real-time PCR检测海马区抑郁相关基因脑源性神经营养因子(BDNF)、五羟色胺转运体(5-HTT)，吲哚胺2，3加双氧酶1（IDO1）及脾脏炎症因子白细胞介素（IL）-1β、IL-6的表达情况。 结果 慢性应激6周后， CRS组小鼠的水平穿格数及直立数无显著变化而CUMS组极显著下降；CRS组与CUMS组小鼠悬尾及强迫游泳试验累计不动时间均显著增加（P<0.05）；同时两种应激均能引起海马和脾脏结构的损伤，但CUMS组海马区的神经元损伤更严重；仅有CUMS组海马区相关基因显著改变；CUMS组脾脏IL-1β，IL-6的基因表达水平显著升高，而CRS组IL-6水平无显著变化。 结论 应激6周后，CRS和CUMS均可不同程度地引起抑郁样症状；从神经免疫学角度观察，CUMS模型的抑郁样症状明显。提示，与CRS模型相比，CUMS模型更能反映机体的抑郁症状。

Objective To explore the difference of chronic restrain stress (CRS) and chronic unpredictable mild stress (CUMS) model in the neuronal/immune system in 45 male C57BL/6 mice through evaluating behavioral alteration, the hippocampus and the spleen structure and related factor expressions，so as to provide certain references for the pathogenesis of depression and early drug screening for antidepressants. Methods Totally 45 mice were randomly divided into control group，CRS group，and CUMS group．After 6 weeks of stress exposure, Behavioral assessment experiments were carried out to detect the behavior changes of mice. HE staining was to examine structural changes in hippocampus and spleen; The Nissl staining was used to explore neuron damage in hippocampus; In addition, the Real-time PCR was used to detect the gene expression of brain derived neurotrophic factor(BDNF),5-hydroxytrypamine transporter(5-HTT), indoleamine 2, 3 dioxygenase 1（IDO1）in hippocampus and inflammation factor IL-1β, IL-6 in spleen. Results Compared with the control group, CRS group had no significant difference in the number of crossing and rearing. However, it was contrary to the CUMS groups; The immobility of tail suspension and forced swimming test were significant increased in both groups; Both stress had a similar damage effect on hippocampus and spleen structure, while CUMS group of hippocampus neuron damage was more serious; Only CUMS group had significant change in the level of gene expression decreased in BDNF and 5-HTT and elevated in IDO1 expression levels; The spleen gene expression levels of IL-1β and IL-6 were significantly increased in CUMS group, while the spleen gene expression levels of IL-6 had no significant change in CRS group. Conclusion The results show that both CRS and CUMS can induce depressive-like behaviors in C57BL/6 mice. From the perspective of neuro-immunology observation, depression symptoms in CUMS model tend to be more obvious. This suggestes that CUMS model may be a better model of depression.