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基于16S rDNA测序研究滋肾疏肝方对围绝经期抑郁症大鼠肠道菌群的影响
Effect of Zishen Shugan Decoction on the intestinal flora of rats with perimenopausal depression based on 16S rDNA high-throughput sequencing
投稿时间:2026-02-09  修订日期:2026-04-08
DOI:
中文关键词:  滋肾疏肝方  围绝经期抑郁症  16S rDNA高通量测序  肠道菌群  脑-肠轴
英文关键词:Zishen Shugan Decoction  perimenopausal depressed  16S rDNA high-throughput sequencing  intestinal flora  brain-gut axis.
基金项目:浙江省中医优势专科建设项目(浙中医药〔2025〕12号);浙江省中青年临床名中医培养项目(浙中医药[2021]22号);宁波市自然科学基金项目(202003N4264)
作者单位邮编
张宇浪 浙江中医药大学附属宁波市中医院 315010
雷梦灵 浙江中医药大学附属宁波市中医院 
钱睿 浙江中医药大学附属宁波市中医院 
邓艳华* 浙江中医药大学附属宁波市中医院 315010
刘宏飞 浙江中医药大学附属宁波市中医院 
龚文波 浙江中医药大学附属宁波市中医院 
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中文摘要:
      目的 基于脑-肠轴探讨滋肾疏肝方对围绝经期抑郁症大鼠肠道菌群的影响。方法 选取SPF级雌性SD大鼠18只,随机分为假手术组、模型组、滋肾疏肝方低、中、高剂量组和阳性对照组,每组3只。除假手术组,其余组行卵巢去势手术,随后采用慢性不可预见性刺激造模。应激同时假手术组和模型组给予生理盐水灌胃;阳性对照组给予盐酸氟西汀和戊酸雌二醇混悬液灌胃;滋肾疏肝方低、中、高剂量组分别灌服滋肾疏肝中药汤剂。连续给药后,采用16S rDNA测序技术检测肠道菌群的丰富度和多样性。结果 在门水平中,厚壁菌门、拟杆菌门、变形菌门是围绝经期抑郁大鼠肠道中最丰富的菌群,在属水平中,毛螺菌属、拟杆菌属、另枝菌属丰度最高。与假手术组相比,模型组厚壁菌门、ε变形菌门、绿弯菌门丰度低于假手术组(P<0.05)。滋肾疏肝方灌胃后,厚壁菌门、ε变形菌门、绿弯菌门分别在低、中(P<0.05)、高(P<0.05)剂量组肠道中丰度均得到改善。功能注释分析显示,中剂量灌胃处理后,光合作用-天线蛋白(P<0.01)和金黄色葡萄球菌感染(P<0.05)通路水平上调,苯乙烯降解(P<0.05)和香叶醇降解(P<0.05)通路水平下调,而高剂量灌胃香叶醇降解上调(P<0.05)。结论 肠道菌群结构和功能的改变是导致围绝经期抑郁发生的重要因素,滋肾疏肝方可在一定程度改善肠道菌群紊乱,优化肠道菌群组成。
英文摘要:
      Objective To explore the effect of Zishen Shugan decoction on the intestinal flora of rats with perimenopausal depression based on 16S rDNA high-throughput sequencing. Methods Eighteen SPF female SD rats were selected and randomly divided into sham operation group (Sham, n = 3), model control group (Model, n = 3), low-dose Zishen Shugan Prescription group (Low, n = 3), middle-dose Zishen Shugan Prescription group (Middle, n = 3), Zishen Shugan Prescription high dose group (High, n = 3) and positive control group (Positive, n = 3). Except for the Sham group, the rest of the groups underwent ovarian ablation surgery, followed by chronic unpredictable stimulation to establish models. At the same time, the Sham group and Model group were given intragastric administration of normal saline; the Positive group were given intragastric administration of fluoxetine hydrochloride and estradiol valerate suspension; the Low group, Middle group and High group were fed with Zishen Shugan decoction respectively. After continuous administration, the richness and diversity of intestinal flora were detected by 16S rDNA sequencing technology. Results At the phylum level, Firmicutes, Bacteroidetes, and Proteobacteria were the most abundant flora in the intestinal of perimenopausal depressed rats, and at the genus level, Lachnospiraceae_NK4A136_group, uncultured_Bacteroidales_bacterium, and Alistipes had the highest abundance. Compared with the Sham group, the abundances of Firmicutes, Epsilonbacteraeota, and Chloroflexi in the Model group were lower than those in the Sham group (P < 0.05). After intragastric administration of Zishen Shugan Recipe, the abundance of Firmicutes, Epsilonproteobacteria, and Chloroflexi was improved in the low, medium (P < 0.05), and high (P < 0.05) dose groups respectively. Functional annotation analysis showed that after intragastric administration of middle dose of Zishen Shugan prescription, the levels of photosynthesis-antenna protein (P < 0.01) and Staphylococcus aureus infection (P < 0.05) related pathways were up-regulated, and the levels of styrene degradation (P < 0.05) and geraniol degradation (P < 0.05) were down-regulated, while high-dose intragastric administration of geraniol degradation was up-regulated (P < 0.05). Conclusion Changes in the structure and function of intestinal flora are important factors leading to perimenopausal depression. Zishen Shugan decoction can improve the disorder of intestinal flora to a certain extent and optimize the composition of intestinal flora.
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