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目的:探究粪菌移植(FMT)应用于抑郁症临床治疗的潜在可能.方法 :19只雄性Sprague-Dawlay大鼠被随机分为三组:对照组(n=6),CUMS组(n=6),和CUMS+FMT组(n=7).后两组大鼠进行为期37天的CUMS联合孤养造模,CUMS+FMT组在建模的后三周每周进行一次FMT.实验采用体重检测、行为学检测、ELISA、免疫组化分析、16S rDNA测序、菌群多样性分析等方法,测定大鼠模型的抑郁相关指标和肠道微生物群组成.结果 :CUMS大鼠体重增加减缓、蔗糖偏好降低、强迫游泳测试中不动时间延长以及肠道菌群结构改变,这些变化在CUMS+FMT组被逆转.ELISA分析显示,FMT一定程度上逆转了抑郁大鼠血清IL-6、TNF的升高及5-HT的下降;免疫组化结果显示,FMT逆转了海马GABA水平下降,但导致海马区谷氨酸水平略有升高.结论 :在大鼠模型中,FMT显著改善了CUMS大鼠的抑郁相关表现,影响了体重增速、抑郁样行为、海马神经递质水平、粪便微生物群组成、炎症反应和血清5-HT水平等.“,”Objective:To determine whether fecal microbiota transplantation(FMT)could play a potential role in treat-ing depression.Methods:Nineteen Male Sprague-Dawlay rats were randomly subdivided into three groups as follows:con-trol group(n=6),chronic unpredictable mild stress(CUMS)group(n=6),and CUMS+FMT group(n=7).Rats in the latter two groups were housed individually and subjected to 37 days of CUMS protocols;those in the last group were subjected to FMT once a week in the last 3 weeks of CUMS protocols.Body mass assessment,multiple behavioral tests,ELISA analysis,im-munohistochemistry,as well as 16S rDNA sequencing and diversity analysis were performed for the determination of depres-sion-like phenotypes and gut microbiota composition in rat models.Results:In the CUMS group,CUMS was associated with an induction in lower weight gain,decreased sucrose preference rate,longer immobility in a forced swimming test,and altered fecal microbiota composition.In contrast,these changes were reversed in the CUMS+FMT group.Moreover,ELISA analysis also showed that FMT reversed CUMS-induced increases in IL-6,and TNF-α,and the decrease in 5-HT serum levels.FMT also reversed the CUMS-induced decrease in GABA levels but led to a slight increase in glutamate levels in the hippocampus.Conclusion:In a rat model,FMT can reverse the CUMS-induced depression-like phenotypes,including alterations in long-term weight gain,depression-like behaviors,hippocampal neurotransmitter levels,fecal microbiota com-position,inflammatory responses and serum 5-HT level.