目的 初步研究纯种发酵淡豆豉的抗抑郁作用及其活性成分。方法 制备自然发酵淡豆豉和枯草芽孢杆菌纯种发酵淡豆豉，采用显色鉴别、薄层鉴别、异黄酮和 γ-氨基丁酸（GABA）的含量测定对纯种发酵淡豆豉进行质量评价；昆明小鼠按体质量随机分为 8 组，每组 10 只，雌雄各半，分别为对照组、模型组、盐酸氟西汀（阳性对照，0.01 g·kg^-1）组、γ-氨基丁酸（GABA，0.014 45 g·kg^-1）组、异黄酮（0.003 05 g·kg^-1）组、自然发酵淡豆豉 醇 提 水 洗 脱 物（水 洗 脱 物 ，1.82 g·kg^-1）组 、自 然 发 酵 淡 豆豉 总 提 物（自 然 发 酵 ，1.82 g·kg^-1）组、纯种发酵淡豆豉总提物（纯种发酵，1.82 g·kg^-1）组，除对照组外，建立慢性温和不可预知应激（CUMS）小鼠抑郁模型，边造模边给药，每日应激前 1 h ig 给药，连续给药 28 d。实验第 0、7、14、21、28 天分别测定各组小鼠体质量，第 28 天给药 1 h 后，进行悬尾、强迫游泳、糖水偏好、敞箱实验各行为学指标检测；HE 染色后观察海马 CA1 区病理学变化；超高效液相色谱-串联质谱法（UPLC-MS/MS）鉴定水洗脱物组、纯种发酵组的主要化学成分。结果 纯种发酵淡豆豉与自然发酵淡豆豉有相同的显色反应、显色斑点和 GABA 含量。与模型组相比，各给药组在应激第 14、21、28 天时体质量增加明显（P＜0.01），悬尾及强迫游泳不动时间显著降低（P＜0.01）；GABA 组、异黄酮组、纯种发酵组、自然发酵水洗脱物组小鼠糖水偏好指数均显著增加（P＜0.05、0.01）；盐酸氟西汀组、水洗脱物组、GABA 组、纯种发酵组小鼠敞箱实验跨格数和直立数均显著增加（P＜0.05、0.01）；各给药组海马 CA1 区细胞排列紧密有序，边缘圆润，细胞间隙正常。纯种发酵组与自然发酵总提物组、水洗脱物组小鼠的各项行为学指标均无显著差异。自然发酵醇提水洗脱物组、纯种发酵总提物组都含有大豆苷元、染料木素、GABA 和各种氨基酸。结论 纯种发酵淡豆豉具有与自然发酵淡豆豉相似的抗抑郁作用，抗抑郁作用的主要成分可能是 GABA 和异黄酮。

Objective A preliminary study on the antidepressant effect of pure-bred fermented Sojae Semen Praeparatum (PF-SSP) and its active components. Methods According to the established process in our laboratory, natural fermented Sojae Semen Praeparatum (NF-SSP) and PF-SSP by Bacillus subtilis were prepared. The quality evaluation of PF-SSP was carried out by colorimetric identification, thin-layer identification, and content determination of flavonoid and γ -aminobutyric acid (GABA). Divided Kunming mice into eight groups randomly by body weight, with 10 mice in each group, half male and half female. The groups were as follows: control group, model group, fluoxetine (positive control, 0.01 g·kg^-1) group, GABA (0.014 45 g·kg^-1) group, flavonoid (0.003 05 g·kg^-1) group, NF-SSP ethanol extract washout material (water washout material, 1.82 g·kg^-1) group, NF-SSP total extract (NF-SSP, 1.82 g·kg^-1) group, PF-SSP total extract group (PF-SSP, 1.82 g·kg^-1). Except for the control group, an experimental model of chronic mild unpredictable stress (CUMS) in mice was established, and the mice were given drugs while being subjected to the model. Drugs were administered ig one hour before the stress every day for 28 consecutive days. Body weight was measured in mice at 0, 7, 14, 21, and 28 days. The behavioral indicators of the hanging tail, forced swimming, sucrose preference, and open field test were detected 1 h after giving drugs on day 28. Hematoxylin and eosin (HE) staining was performed to observe pathological changes in the hippocampal CA1 area. UPLC-MS/MS was used to identify the main chemical components of the aqueous extract and pure strain fermentation products. Results PF-SSP and NF-SSP had the same color reaction, color spots and GABA content. Compared with model group, the body weight of each treatment group increased significantly at 14, 21, and 28 days after stress (P<0.01), and the immobility time in the tail suspension and forced swimming test were significantly reduced (P<0.01); the sucrose preference index of GABA group, isoflavone group, PF-SSP group, and water washout group mice were significantly increased (P<0.05, 0.01); the number of grid crossings and standing up in the open field test of fluoxetine hydrochloride group, washout group, GABA group, and PF-SSP group mice were significantly increased (P<0.05, 0.01); the cells in the CA1 region of the hippocampus in each treatment group were arranged tightly and orderly, with smooth edges and normal cell gaps. The behavioral indices of the pure fermentation group and the natural fermentation total extract group were not significantly different from those of the model group. The natural fermentation ethanol extract washout group and the pure fermentation total extract group both contained daidzein, genistein, GABA, and various amino acids. Conclusion PF-SSP had the similar antidepressant effect as NF-SSP, the main components of antidepressant effect may be GABA and isoflavones.

R285.5

国家自然科学基金资助项目（82060709，82360772）；江西省教育厅科学技术研究项目（GJJ180655）