大鼠肥胖抑郁模型建立及肠道菌群多样性的性别差异研究

Establishment of an obesity depression model in rats and study of sex differences in gut flora diversity

目的 肥胖抑郁大鼠模型建立并对比研究肠道菌群多样性的变化。方法 采用高脂饲料喂养和CUMS经典造抑郁方法建立肥胖抑郁模型。将SD大鼠随机分为正常组(C组)、单纯肥胖组(F组)、单纯抑郁组(Y组)和肥胖抑郁组(FY组),整个造模持续5个月,通过糖水偏好实验、旷场实验和强迫游泳实验来评估大鼠抑郁样行为,检测模型鼠血清雌激素水平和血脂4项,并采集各组大鼠粪便样品,通过16S rDNA高通量测序法和生物信息分析软件分析测序结果,比较各组大鼠肠道菌群多样性的变化。结果 高脂饮食和CUMS方法成功制作肥胖抑郁鼠模型,肥胖和肥胖抑郁雌性大鼠雌激素水平明显升高,而雄性各组间雌激素水平无显著性差异。雌雄鼠的FY组肠道菌群α多样性具有显著差别,拟杆菌门和厚壁菌门B/F比值下降,且雄鼠肥胖抑郁B/F值只有雌鼠的一半左右。在属水平,研究结果表明雌雄鼠FY组和F组肠道菌群中Blautia等8个菌群变化一致,但是雌性与雄性在拟杆菌属等各有少量菌群的变化不一致。雌雄肥胖抑郁模型中,肠道菌群革兰氏阳性菌和阴性菌的组成出现差异,G+的构成,雌性和雄性均由由厚壁菌门和放线菌门构成,但构成比例不一样。G-雄性主要由厚壁菌门、拟杆菌和脱硫杆菌构成,雌性的G-主要由拟杆菌门、疣状体菌门和脱硫杆菌构成,构成比也不一样。结论 通过高脂饮食和CUMS联合孤养可以建立肥胖抑郁模型,但雌雄肥胖抑郁大鼠肠道菌群的组成不一致。

Objective To compare changes in microbial diversity in the intestines of male and female rats with obesity and depression.Methods An obesity and depression model was established by feeding rats a high fat diet and the cums classic depression making method.SD rats were randomly divided into control group(Group C),obese group(Group F),the depression group(Group Y),the obesity and depression group(Group FY).Five months were required for modeling.Depression-like behavior was evaluated by the sugared water preference test,open field test,and forced swimming test.The serum estrogen level and blood lipids were measured.Fecal samples were also collected.High-throughput sequencing of 16S rDNA was performed and the result were analyzed by bioinformation analysis software.Changes in intestinal flora diversity of rats in each group were compared.Results Obesity depression model rats were successfully established by a high-fat diet and cums method in the same countries.The estrogen level of obesity and obesity depression female rats was significantly increased,while there no significant difference was observed in the estrogen level between male groups.There was a significant difference in diversity of intestinal flora in Group FY.The B/F value was lower than that of in obesity and depression groups,and the B/F value of obesity and depression in male rats was only approximately half that of female rats.At the genus level,changes in Blautia and the other eight flora in the Group FY and Group F of male and female rats were consistent,but changes in a small number of flora in Bacteroides and other genera in females and males were inconsistent.In the male and female obesity and depression model,there were differences in the composition of Gram-positive and-negative bacteria among the intestinal flora.The composition of G+was Firmicutes and actinomycetes,but the proportions were different.G-males mainly had Firmicutes,Bacteroides,and desulfitobacteria,whereas females mainly had Bacteroides,verruciformis,and desulfitobacteria with different composition ratios.Conclusions Significant changes in the composition and structure of intestinal flora in male and female obese and depressed rats may be related to estrogen.