| 甘麦大枣汤联合氟西汀通过调控肠道菌群改善慢性应激小鼠抑郁症状的研究 |
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| 作者姓名： | 郑劼 许一凡 陈艳燕 周祎靖 张雨恒 余雪瑞 洪敏 |
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| 作者单位： | 1.南京中医药大学药学院，江苏省中药药效与安全性评价重点实验室，江苏 南京〓210023; |
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| 摘 要： | 目的 研究甘麦大枣汤（GMZ）联合氟西汀（Flx）是否通过调控小鼠肠道菌群改善慢性应激小鼠抑郁症状。方法 采用慢性不可预见性轻度应激（CUMS）联合孤养复制小鼠CUMS抑郁模型，观察GMZ（7 g/kg）、Flx（10 mg/kg）、GMZ（7 g/kg）+Flx（10 mg/kg）灌胃给药对小鼠体质量、糖水偏好百分比、尾悬累积静止不动时间、旷场水平运动次数及脑内5-HT水平的影响；采用16S rDNA测序方法分析CUMS小鼠肠道菌群丰度和结构；采用粪菌移植实验评价移植GMZ+Flx粪菌对CUMS小鼠抑郁行为及脑内5HT水平的影响。 结果 CUMS应激联合孤养可成功复制小鼠慢性应激CUMS抑郁模型；GMZ+Flx给药能显著提高CUMS小鼠体质量（P<0.01）及糖水偏好百分比（P<0.01）、降低尾悬实验累积静止不动时间（P<0.01）、增加旷场实验水平运动次数（P<0.05）、提高小鼠脑5HT的水平（P<0.01）；与正常组相比，CUMS组小鼠肠道菌群门水平上拟杆菌门（Bacteroidetes）相对丰度显著下降（P<0.01）、厚壁菌门（Firmicutes）相对丰度明显升高（P<0.01），GMZ给药可显著降低门水平Firmicutes相对丰度（P<0.05），对Bacteroidetes相对丰度有升高趋势；在CUMS造模基础上，移植GMZ+Flx粪菌，可显著提高CUMS小鼠糖水偏好百分比（P<0.01）、降低尾悬累积静止不动时间（P<0.05）、增加旷场水平运动次数（P<0.01）、提高小鼠脑5HT的水平（P<0.01）。此外，灌胃给药及粪菌移植实验均显示，GMZ对CUMS小鼠尾悬实验改善显著，Flx对旷场水平运动次数改善明显。结论 甘麦大枣汤联合氟西汀通过调控肠道菌群改善慢性应激小鼠抑郁症状。
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| 关 键 词： | 甘麦大枣汤 氟西汀 慢性应激抑郁模型 肠道菌群 |
Ganmai Dazao Decoction Combined with Fluoxetine Treatment Alleviates Depressive Symptoms in Chronic Stress Mice by Modulating Intestinal Microbiota |
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| Authors: | ZHENG Jie XU Yi-fan CHEN Yan-yan ZHOU Yi-jing ZHANG Yu-heng YU Xue-rui HONG Min |
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| Affiliation: | 1.School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China2.School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China |
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| Abstract: | OBJECTIVE To investigate whether Ganmai Dazao Decoction (GMZ) combined with fluoxetine (Flx) treatment can alleviate depressive symptoms in chronic stress mice by modulating intestinal microbiota. METHODS Chronic unpredictable mild stress (CUMS) with solitary raise was employed to establish a chronic stress mice model. Mice body weight, sucrose preference, tail suspension test (TST), open field test (OFT), and brain 5HT level were evaluated to clarify the efficacy of GMZ (7 g/kg), Flx (10 mg/kg), or GMZ (7 g/kg)+Flx (10 mg/kg) with intragastric administration in CUMS mice. 16S rDNA sequencing was used to analyze the changes of intestinal microbial abundance and structure in CUMS mice. The effects of transplantation with GMZ+Flx group fecal bacteria on depressive behavior and the brain 5HT level in CUMS mice were assessed by fecal bacteria transplantation experiments.RESULTS The chromic stress mice model was successfully reproduced by CUMS stress with solitary raise. GMZ combined with Flx treatment could significantly increase the bodyweight (P<0.01) and sucrose preference percentage (P<0.01), reduce the immobility time of TST (P<0.01), increase the horizontal locomotor of OFT (P<0.05), and increase the level of brain 5-HT (P<0.01) in CUMS mice compared with control mice. In addition, compared with control mice, the relative abundance of Bacteroidetes in intestinal microbiota of mice in CUMS group was significantly decreased (P<0.01), and that of Firmicutes was significantly increased (P<0.01). However, the relative abundance of Firmicute was reduced notably (P<0.05) and Bacteroidetes was increased mildly in GMZ-treated mice. Furthermore, compared with CUMS mice, GMZ+Flx treatment fecal bacteria transplantation significantly increased the percentage of sucrose preference (P<0.01), reduced the immobility time of TST (P<0.05), increased the horizontal locomotor of OFT (P<0.01), and increased the level of brain 5-HT (P<0.01). Moreover, both intragastric administration and fecal bacteria transplantation experiments showed that GMZ reduced the immobility time of TST in CUMS mice remarkably, whereas Flx increased the horizontal locomotor of OFT obviously. CONCLUSION GMZ combined with fluoxetine treatment can alleviate the depressive symptoms of chronic stress mice by modulating intestinal microbiota. |
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| Keywords: | Ganmai Dazao Decoction fluoxetine chronic stress depressive model intestinal microbiota |
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