目的 利用16S rRNA高通量测序技术研究柴归颗粒对慢性不可预知温和刺激（chronic unpredicted mild stress，CUMS）抑郁大鼠模型肠道菌群的调节作用，探讨柴归颗粒的抗抑郁作用及机制。方法 SD大鼠随机分为对照组、模型组和柴归颗粒（8.3 g/kg）组，给药1 h后造模，持续28 d。收集大鼠肠道内容物，提取总DNA，根据细菌16S rRNA V3~V4区设计引物进行扩增，利用Illumina Miseq平台进行高通量测序。结果 与对照组比较，模型组大鼠肠道菌群栖热菌门（Thermi）、变形菌门（Proteobacteria）、拟杆菌门（Bacteroidetes）和放线菌门（Actinobacteria）相对丰度水平显著降低（P<0.05），乳酸杆菌属Lactobacillus相对丰度水平显著升高（P<0.05），栖热菌属Thermus、不动杆菌属Acinetobacter、甲基杆菌属Methylobacterium、青枯菌Ralstonia、纤毛菌属Leptothrix、假单胞菌属Pseudomonas、棒状杆菌属Corynebacterium和苍白杆菌属Ochrobactrum相对丰度水平显著降低（P<0.05）。与模型组比较，柴归颗粒可调节CUMS大鼠肠道菌群的构成，显著回调栖热菌门、变形菌门、拟杆菌门和放线菌门相对丰度水平（P<0.05、0.01），显著降低乳酸杆菌属相对丰度水平（P<0.01），显著升高栖热菌属、不动杆菌属、甲基杆菌属、青枯菌属、纤毛菌属和苍白杆菌属相对丰度水平（P<0.01）。结论 柴归颗粒可能通过调节参与精氨酸代谢途径的肠道菌群发挥抗抑郁作用。

Objectives To study the effect of Chaigui Granule (柴归颗粒) on gut microbiota in chronic unpredictable mild stress (CUMS)-induced depression rats model by 16S rRNA gene sequencing, and to explore the mechanism of antidepressant of Chaigui Granule. Methods Rats were randomly divided into control group, model group, and Chaigui Granule (8.3 g/kg) group, model was established after administration 1 h and lasted for 28 d. Rat intestinal contents were collected and total DNA was extracted. Primers based on bacterial 16S rRNA V3-V4 regions were design for amplification, and Illumina Miseq platform was used for high-throughput sequencing. Results Compared with control group, relative abundance levels of Thermi, Proteobacteria, Bacteroidetes and Actinobacteria of intestinal flora in model group were significantly reduced (P<0.05), relative abundance level of Lactobacillus was significantly increased (P<0.05), relative abundance levels of Thermus, Acinetobacter, Methylobacterium, Ralstonia, Leptothrix, Pseudomonas, Corynebacterium, and Ochrobactrum were significantly reduced (P<0.05). Compared with model group, Chaigui Granule adjusted the composition of intestinal flora in CUMS rats, and significantly adjusted the relative abundance levels of Thermi, Proteobacteria, Bacteroides and Actinobacteria (P<0.05, 0.01), significantly reduced the relative abundance level of Lactobacillus (P<0.01), and significantly increased the relative abundance levels of Thermus, Acinetobacter, Methylobacterium, Ralstonia, Leptothrix, and Ochrobactrum (P<0.01). Conclusion Chaigui Granule may play an antidepressant effect by regulating the intestinal flora involved in arginine metabolism.

R285.5

国家“重大新药创制”科技重大专项（2017ZX09301047）；山西省科技厅重点研发计划项目（201903D321210）；山西省重点研发计划项目（201603D3113013）