氟西汀对抑郁模型大鼠肠道菌群代谢多样性的影响  

Effect of Fluoxetine on Metabolic Diversity of Intestinal Microbiota in Rats With Depression

作　　者：李宇 蔡萧君 陆振华 颉彦鹏 王涛[1] 王钦 吴圆圆 LI Yu;CAI Xiaojun;LU Zhenhua;XIE Yanpeng;WANG Tao;WANG Qin;WU Yuanyuan(Department of Endocrinology,Heilongjiang Provincial Hospital of Traditional Chinese Medicine,Harbin,150036;Department of Gastroenterology,Heilongjiang Provincial Hospital of Traditional Chinese Medicine,Harbin,150036)

机构地区：[1]黑龙江省中医医院内分泌科,150036 [2]黑龙江省中医医院消化内科,150036

出　　处：《胃肠病学》2021年第6期342-347,共6页Chinese Journal of Gastroenterology

基　　金：黑龙江省应用技术研究与开发计划项目(GA19C108)。

摘　　要：背景:研究表明肠道菌群与抑郁的发生、发展密切相关,经典抗抑郁药氟西汀对肠道菌群的调控机制尚不明确。目的:探讨氟西汀调控抑郁模型大鼠肠道菌群结构和代谢多样性的机制。方法:将30只SD大鼠随机分为空白组、模型组、氟西汀组,采用慢性不可预知温和应激(CUMS)联合孤养建立抑郁大鼠模型,氟西汀组给予盐酸氟西汀分散片3.17 mg·kg^(-1)·d^(-1)灌胃,空白组和模型组给予蒸馏水灌胃。8周后提取肠道微生物,采用Biolog-ECO系统和选择性培养分析大鼠肠道菌群结构和代谢变化规律。结果:抑郁模型大鼠肠道菌群结构和代谢多样性发生显著变化。氟西汀可显著上调模型大鼠肠道中双歧杆菌丰度,下调脆弱拟杆菌、肠球菌、肠杆菌和产气荚膜梭菌丰度,而对乳杆菌丰度无明显调节作用。模型组肠道菌群Shannon指数、Shannon均匀度、Simpson指数和Mclntosh指数均显著降低(P<0.01),氟西汀可显著上调Shannon指数和Mclntosh指数(P<0.01)。聚类分析和主成分分析显示氟西汀组与空白组、模型组之间存在明显差异。结论:氟西汀对抑郁模型大鼠肠道菌群结构和代谢多样性具有显著正向调控作用,与其抗抑郁机制具有相关性。Background:Studies have shown that intestinal microbiota is closely related to the occurrence and development of depression,however,the regulatory mechanism of the classic antidepressant fluoxetine on intestinal microbiota is still unclear.Aims:To investigate the mechanism of fluoxetine in regulating intestinal microbiota structure and metabolic diversity in rats with depression.Methods:Thirty SD rats were randomly divided into blank group,model group and fluoxetine group.Depression rat model was established by chronic unpredictable mild stress(CUMS)combined with solitary care.Fluoxetine hydrochloride dispersible tablets 3.17 mg·kg^(-1)·d^(-1) was administrated intragastrically in fluoxetine group,and distilled water was administrated intragastrically in blank group and model group.After 8 weeks,intestinal microbiota were extracted,and the structure and metabolic changes of intestinal microbiota were analyzed by Biolog-ECO system and selective culture.Results:The structure and metabolic diversity of intestinal microbiota were significantly changed in the depression model rats.Fluoxetine could significantly up-regulate the abundance of Bifidobacterium and down-regulate the abundance of Bacteroides fragilis,Enterococcus,Enterobacter and Clostridium perfringens in intestinal tract of model rats,but had no significant effect on the abundance of Lactobacillus.The intestinal microbiota Shannon index,Shannon evenness,Simpson index and Mclntosh index in model group were significantly decreased(P<0.01),and fluoxetine could significantly increase Shannon index and Mclntosh index(P<0.01).Cluster analysis and principal component analysis showed significant differences among fluoxetine group,blank group and model group.Conclusions:Fluoxetine has a significant positive regulation effect on intestinal microbiota structure and metabolic diversity of depression model rats,which is related to its antidepressant mechanism.

关 键 词：氟西汀 肠道菌群 抑郁 代谢多样性 Biolog-ECO 

分 类 号：R28[医药卫生—中药学]