【摘要】 目的 采用抗生素鸡尾酒法对肥胖小鼠连续灌胃7 d,评估构建伪无菌肥胖小鼠模型的可行性。方法 将60只健康雄性C57BL/6小鼠随机分为对照组(n=10)与造模组(n=50),利用高脂饮食诱导造模组形成肥胖小鼠模型。从肥胖小鼠模型中随机选取10只肥胖小鼠纳入抗生素组，其余肥胖小鼠剔除。抗生素组采用生理盐水配制成含20 mg/mL氨苄西林、20 mg/mL甲硝唑、20 mg/mL新霉素和10 mg/mL万古霉素的混悬液，对照组使用生理盐水，按0.1 mL/10 g体积灌胃。收集干预前后小鼠粪菌进行16S rRNA测序。结果 高脂饮食成功诱导小鼠肥胖，11周末造模组体重较对照组增加20%以上(P<0.05)。抗生素干预对小鼠摄食饮水无明显影响(P>0.05),但使肝脏脏器系数增加(P<0.05)。16S rRNA测序结果显示，抗生素组Shannon多样性指数较干预前降低(P<0.001),而对照组无明显变化(P=0.148)。主坐标分析显示抗生素组菌群结构呈离散趋势，与对照组紧密聚集形成鲜明对比。差异分析发现，抗生素干预前主要优势菌群为毛螺菌科和拟杆菌属，干预后转变为肠杆菌科和支原体科。结论 抗生素鸡尾酒法可有效清除肥胖小鼠肠道内的大部分肠道菌群，能够构建伪无菌肥胖小鼠模型。更多还原

【Abstract】 Objective To evaluate the feasibility of constructing a pseudo-aseptic obese mouse model by injecting the obese mice with an antibiotic cocktail for 7 days. Methods 60 healthy male C57BL/6 mice were randomly divided into a control group(n=10) and a model group(n=50). A high-fat diet-induced the model group to form an obese mouse model. 10 obese mice were randomly selected from the obese mouse model to be included in the antibiotic group, and the other obese mice were excluded. In the antibiotic group, normal saline was prepared into a suspension containing 20 mg/mL ampicillin, 20 mg/mL metronidazole, 20 mg/mL neomycin, and 10 mg/mL vancomycin. In contrast, the control group was given normal saline and gavage at a volume of 0.1 mL/10 g. 16S rRNA was sequenced before and after the intervention. Results A high-fat diet successfully induced obesity in mice, with the model group showing a weight increase of over 20% compared to the control group by the 11th week(P<0.05). Antibiotic intervention had no significant effect on food and water intake in mice(P>0.05), but it significantly increased the liver organ coefficient(P<0.05). 16S rRNA sequencing results showed that the shannon diversity index in the antibiotic group was lower than before intervention(P<0.001), while the control group showed no significant changes(P=0.148). Principal coordinate analysis showed that the microbiota structure in the antibiotic group exhibited a dispersed trend, in sharp contrast to the tightly clustered structure in the control group. Differential analysis revealed that the predominant bacterial groups before antibiotic intervention were the Fusobacterium and the Bacteroides, which shifted to the Enterobacteriaceae and the Mycoplasmataceae after intervention. Conclusion Antibiotic cocktails can effectively remove most of the intestinal flora in obese mice and can build a pseudo-sterile obese mouse model.更多还原