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目的:探究柴胡疏肝散(Chaihu-Shugan San，CSS)对慢性不可预知性温和应激(chronic unpredictable mild stress，CUMS)致抑郁小鼠行为及神经再生功能的影响。方法:将30只清洁级健康雄性C57BL/6成年小鼠按照随机数字表法分为空白组(Con组)、模型组(CUMS组)、柴胡疏肝散组(CSS组)，每组10只。CUMS组和CSS组小鼠采用CUMS法建立抑郁模型，造模同时分别给予蒸馏水和CSS(2.7 g/kg)灌胃，Con组小鼠只给予等体积蒸馏水灌胃，不进行CUMS刺激。干预结束后，采用体质量增量、糖水偏爱实验、强迫游泳实验和悬尾实验检测小鼠抑郁样行为。采用免疫荧光染色法检测海马齿状回新生神经元数量。qRT-PCR法检测小鼠海马组织中脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)、成纤维细胞生长因子2(fibroblast growth factor 2，FGF2)、纺锤体与动粒相关复合物2(spindle and kinetochore-associated protein 2，SKA2)mRNA表达水平。采用SPSS 22.0软件进行统计分析，多组间比较采用单因素方差分析，进一步两两比较采用Tukey检验。结果:(1)三组小鼠在造模后的体质量增量差异有统计学意义(n F＝8.859，n P<0.05)，CUMS组小鼠的体质量增量低于Con组和CSS组(均n P<0.05)。三组小鼠在行为学测试中的糖水偏爱率、悬尾不动时间和游泳不动时间均差异有统计学意义(n F＝10.544，12.957，8.095，均n P<0.05)。CUMS组小鼠的糖水偏爱率低于Con组[(87.46±2.78)%，(93.90±3.31)%，n P<0.05]，CSS组小鼠的糖水偏爱率[(91.65±2.61)%]则高于CUMS组(n P<0.05)。CUMS组小鼠悬尾不动时间[(198.00±27.57)s]和游泳不动时间[(322.20±46.98)s]均高于Con组[悬尾不动时间(138.80±38.50)s，游泳不动时间(238.50±50.51)s，均n P<0.05]。CSS组小鼠的悬尾不动时间[(139.00±21.29)s]和游泳不动时间[(265.20±44.90)s]均低于CUMS组(均n P<0.05)。(2)免疫荧光染色结果显示，三组小鼠海马齿状回BrdU与NeuN双标的细胞数量差异有统计学意义(n F＝9.486，n P<0.05)。CUMS组小鼠双标染色细胞数量[(31.66±3.21)个/视野]低于Con组[(63.66±15.17)个/视野]和CSS组[(58.00±6.00)个/视野](均n P<0.05)。(3)qRT-PCR结果显示，三组小鼠海马齿状回BDNF、FGF2和SKA2的mRNA水平均差异有统计学意义(n F＝14.522，9.337，8.701，均n P<0.05)。CUMS组小鼠海马齿状回BDNF mRNA(0.79±0.06)、FGF2 mRNA(0.74±0.18)和SKA2 mRNA(0.52±0.32)的相对表达量均低于Con组[BDNF mRNA(1.03±0.10)，FGF2 mRNA(1.04±0.11)，SKA2 mRNA(1.05±0.37)，均n P<0.05]。与CUMS组相比，CSS组BDNF mRNA(1.07±0.80)、FGF2 mRNA(1.30±0.29)、SKA2 mRNA(1.40±0.55)相对表达水平均较高(均n P<0.05)。n 结论:柴胡疏肝散能缓解抑郁模型小鼠的抑郁症状，其机制可能与提高海马区BDNF、FGF2、SKA2 mRNA的表达并促进神经干细胞增殖有关。“,”Objective:To explore the effects of Chaihu-Shugan San (CSS) on the behavior and neurogenesis function of depression model mice induced by chronic unpredictable mild stress (CUMS).Methods:Thirty clean grade healthy male C57BL/6 adult mice were randomly divided into control group (Con group), model group (CUMS group) and Chaihu-Shugan San treatment group (CSS group), with 10 mice in each group.The mice in CUMS group and CSS group were given CUMS intervention to establish depression model. At the same time of modeling, the mice in CUMS group and CSS group were given distilled water and CSS(2.7 g/kg) by gavage respectively.While the mice in Con group were only given equal volume distilled water by gavage without CUMS stimulation.After the intervention, the depressive-like behavior of mice was evaluated by increased body weight, sugar water preference test (SPT), forced swimming test (FST) and tail suspension test (TST). The number of newborn neurons was detected by immunofluorescence staining. The mRNA expression levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and spindle and kinetochore-associated protein 2(SKA2) in mice hippocampus were detected by qRT-PCR.Statistical analysis was performed by SPSS 22.0 software. One-way ANOVA was used for multi group comparison, and Tukey test was used for pairwise comparison.Results:(1) After modeling, there was significant difference in body weight increment among the three groups (n F=8.859, P <0.05). The body weight increment of CUMS group was lower than those of Con group and CSS group (both n P< 0.05). There were significant differences in sugar water preference rate, tail suspension immobility time and swimming immobility time among the three groups (n F=10.544, 12.957, 8.095, all n P<0.05). The sugar water preference rate in CUMS group was lower than that in Con group ((87.46±2.78)%, (93.90±3.31)%,n P<0.05), and that in CSS group was higher than that in CUMS group ((91.65±2.61)%)(n P<0.05). The tail suspension immobility time ((198.00±27.57) s) and swimming immobility time ((322.20±46.98) s) in CUMS group were higher than those in Con group ((138.80±38.50) s, (238.50±50.51) s, bothn P<0.05). The tail suspension immobility time ((139.00±21.29) s) and swimming immobility time ((265.20±44.90) s) in CSS group were lower than those in CUMS group (bothn P<0.05). (2) Immunofluorescence showed that there was significant difference in the number of newborn neurons labeled by BrdU and NeuN in the dentate gyrus of hippocampus among the three groups (n F=9.486, n P<0.05). The number of double labeled cells (31.66±3.21) in CUMS group was lower than that in Con group(63.66±15.17) and CSS group (58.00±6.00) (bothn P<0.05). (3) RT-PCR results showed that the mRNA levels of BDNF, FGF2, SKA2 in hippocampal dentate gyrus of the three group were significantly different(n F=14.522, 9.337, 8.701, all n P<0.05). The levels of BDNF mRNA (0.79±0.06), FGF2 mRNA (0.74±0.18) and SKA2 mRNA (0.52±0.32) in the dentate gyrus of hippocampus in CUMS group were lower than those in Con group (BDNF mRNA (1.03±0.10), FGF2 mRNA (1.04±0.11), SKA2 mRNA (1.05±0.37), alln P<0.05). Compared with CUMS group, the mRNA levels of BDNF (1.07±0.80), FGF2 (1.30±0.29) and SKA2 (1.40±0.55) in CSS group were higher (alln P<0.05).n Conclusion:CSS can alleviate the depressive like behavior of depression model mice, which may be related with increasing the mRNA expression levels of BDNF, FGF2, SKA2 and promoting the proliferation of neural stem cells in hippocampus.