人源化更年期抑郁小鼠模型构建及评价

Establishment and evaluation of a humanized depression mouse model

目的通过粪菌移植技术构建人源化抑郁小鼠模型,并对模型进行评价。方法将更年期抑郁人群和健康人群的粪便移植给“模拟无菌”小鼠,先将60只C57BL/6小鼠分为空白组、抑郁粪菌移植FMT-P组和健康粪菌移植FMT-H组。空白组(n=20)仅予普通饲料喂养;FMT-P组(n=20)采用抗生素鸡尾酒疗法预处理,再进行抑郁人群粪菌移植制作模型;FMT-H组(n=20)则给予抗生素鸡尾酒疗法,再进行健康人群粪菌移植制作模型,均持续28 d。观察大鼠的一般情况和行为学检测(悬尾实验、新环境进食实验、糖水偏爱实验),ELISA测定血清多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)、γ氨基丁酸(GABA)的水平,HE染色观察结肠组织病理。结果与空白组及FMT-H组相比,FMT-P组小鼠体重增长较慢,绝望时间明显延长,摄食时间及糖水偏好率明显下降,并伴有活动减少、毛发蓬乱发黄无泽、易掉落、精神萎靡倦怠等抑郁症状;其血清GABA含量、5-HT含量、DA含量显著降低,镜下可见结肠组织排列紊乱,腺体增多,局部炎性细胞浸润。结论抗生素鸡尾酒疗法结合粪菌移植技术可建立人源化抑郁小鼠模型。

Objective To establish a humanized mouse model of depression by fecal bacteria transplantation and evaluate the model.Methods The feces of depressed and healthy people in the climacteric period were transplanted into simulated sterile mice.Sixty C57BL/6 mice were divided into blank group,depressed fecal bacteria transplantation(FMT-P)and healthy fecal bacteria transplantation(FMT-H)a groups.The blank group(20 mice)was only fed an ordinary diet.The FMT-P group(20 mice)was pretreated with an antibiotic cocktail,and then the model was established by fecal bacteria transplantation in the depressed population.The FMT-H group(20 mice)was administered the antibiotic cocktail,and then the model was established by fecal bacteria transplantation in the healthy population.Each group was continuously fed for 28 days.The general conditions and behavioral tests of mice were observed by tail suspension and new environment feeding tests,the serum levels dopamine(DA),norepinephrine(NE),5-hydroxytryptamine(5-HT),and γ-aminobutyric acid(GABA)were determined by ELISA,and colon histopathology was observed by HE staining.Results Compared with the blank control group,the body mass of the FMT-P group was increased slowly,the time of depression was significantly prolonged,the feeding time was significantly decreased,and there were depression symptoms such as decreased activity,disheveled and yellow hair,shedding fur easy to fall off,and mental fatigue.The serum levels of GABA,5-HT,and DA in FMT-P group the group were significantly lower than those in the blank control group.Microscopically,colonic tissue was disordered,glands enlarged glands were increased,and local inflammatory cells had infiltrated.Conclusions The combination of antibiotic cocktail therapy and fecal bacteria transplantation establishes a humanized mouse model of depression.