不同品系小鼠肥胖哮喘模型建立及比较

Establishment and comparison of obese asthma models in different strains of mice

目的建立并比较不同品系小鼠营养性肥胖哮喘模型。方法选用KM、C57BL/6J、BALB/c3个品系♀小鼠,随机分为对照组、哮喘组、肥胖组、肥胖哮喘组,分别以高脂饲料或普通饲料饲喂12周后,以卵清蛋白(OVA)或磷酸盐缓冲液(PBS)致敏激发小鼠,实验终点测定小鼠体重、身长、脂肪重量、肝脏重量、Lee's指数、血清总胆固醇(TC)及甘油三酯(TG)水平、支气管肺泡灌洗液(BALF)中OVA特异性IgE浓度。观察各组脂肪细胞形态及气道病理学改变。测定各组小鼠的特殊气道阻力(sRaw)。结果 KM肥胖组体重及Lee's指数增长最快,但哮喘特征性表现不明显;C57BL/6J小鼠能形成哮喘特征性表现,但肥胖相关指标差异无显著性;BALB/c肥胖组小鼠肥胖指标较之正常组差异有显著性。经OVA致敏激发后,BALB/c小鼠显示出更加明显的哮喘症状、气道高反应性和气道炎症表现。结论 BALB/c小鼠经高脂饲料诱导,OVA致敏激发能形成良好的肥胖合并哮喘模型。

Aim To establish and compare asthma models among different strains of obese mice.Methods Different strains of SPF female mice,namely Kunming(KM),C57BL/6J and BALB/c mice,were randomly divided into four groups(control group,asthma group,obesity group and obese asthma group).The mice were fed a high-fat diet or a normal diet for 12 weeks,following which they were sensitized and challenged with ovalbumin(OVA) or phosphate-buffered saline(PBS).Body weight,fat weight,liver weight,Lee's index,OVA-specific IgE concentration in bronchoalveolar lavage fluid(BALF),serum total cholesterol(TC) and triglyceride(TG) levels,and lung and adipose morphologies were evaluated.The specific airway resistance(sRaw) was measured using double-chamber plethysmography.Results The mice on a high-fat diet showed a more rapid increase in body weight compared with those on a normal diet.After 12 weeks of feeding,body,fat,and liver weights and Lee's index were higher for the obese mice than for the lean mice.The adipocyte cross-sectional area was significantly greater in the obese BALB/c and KM mice than in their lean counterparts;the C57BL/6J groups showed no significant differences.The BALB/c mice demonstrated more significant symptoms of acute asthma,local inflammation and airway hyper-responsiveness(AHR).Conclusion Compared with C57BL/6J and KM mice,BALB/c mice fed a high-fat diet and sensitized and challenged with OVA provide the most suitable model for evaluating the relationship between obesity and asthma.