饮食诱导小鼠肥胖模型中胃食管黏膜的变化研究

The effect of high-fat diet-induced obesity on esophagus and stomach in mice

目的建立高脂饮食诱导的小鼠肥胖模型,探讨由肥胖引起的胃食管反流病(GERD)发病基础,并为肥胖与GERD相关性研究提供依据。方法运用Microsoft Office Excel软件把已编号的16只雄性SPF级昆明小鼠随机分2组,每组8只,即饮食诱导肥胖(DIO)组和正常对照(NC)组。喂饲DIO组小鼠高脂饲料,而NC组给予普通的标准饲料喂饲,其余时间2组小鼠在相同环境中自由饮水摄食,实验持续8周。实验结束后通过葡萄糖耐量试验(GTT)、胰岛素耐受试验(ITT)、小鼠胃食管组织及血清检测脂代谢相关血生化指标,同时在光学显微镜下观察胃食管黏膜组织学改变。结果 DIO组小鼠有75%发育为DIO,其体质量增加量为(23. 16±2. 82) g,明显高于NC组小鼠(13. 40±1. 31) g,2组差异具有统计学意义(P <0. 05); DIO组小鼠出现糖耐量异常及胰岛素抵抗现象;通过ELIS法检测血生化指标显示,DIO组小鼠总胆固醇、低密度脂蛋白水平明显高于NC组(P <0. 05),但甘油三酯水平2组无显著差异(P> 0. 05)。DIO组小鼠胃食管黏膜可见增生及炎症细胞的浸润现象。结论 DIO小鼠模型模拟了人类肥胖症患者的体重增长过程,同时适合于评价肥胖所诱导GERD过程所引起的变化,以期为今后进一步研究肥胖引起GERD的机制提供借鉴。

Objective To discuss the diet induced obesity（DIO）on gastroesophageal changes in mice for investigating the role of obesity in the pathogenesis of gastroesophageal reflux disease,and provide with simple and effective experimental basis. Methods 16 male KunMing mice were randomly divided into two groups which are DIO and normal control（NC）group using Microsoft Office Exel.Mice in DIO group were given to high-fat diet,while NC group was given normal diet.After 8 weeks of experiment,glucose tolerance test（GTT）and insulin tolerance test（ITT）were performed firstly,and esophagus,stomach and blood sample of all mice were taken for further detecting the parameters and analyzing histological changes in tissues through HE staining. Results 75% of mice in experimental group improved to DIO and body weight increment of mice in DIO group is（23.16±2.82）g,significantly higher than that of NC group（13.40±1.31）g（ P 〈0.05）.GTT and ITT showed that DIO group happened impaired glucose tolerance and insulin resistance.The result of ELISA indicated that the level of total cholesterol and low density lipoprotein in DIO group were significantly higher than those of NC mice（ P 〈0.05）,but the level of triglyceride has no significant difference between two groups（ P 〉0.05）.Histological changes appeared in DIO group include hyperplasia and infiltration of inflammatory cells in gastroesophageal mucosa. Conclusion DIO model in mice has imitated the process of obesity happens in humans,and it′s appropriate to evaluate obesity induced GERD through this model.Our study provides with not only simple,but also effective experimental basis which has referential value on the research of investigating the role of obesity in the pathogenesis of GERD.