变应性气道反应与抗生素诱导的肠道菌群失调关系研究  

Allergic airway response associated with the intestinal microflora disruption induced by antibiotic therapy

作　　者：刘崇海[1] 杨锡强[1] 刘春花[1] 何云[1] 王莉佳[1] 

机构地区：[1]重庆医科大学附属儿童医院免疫实验室,400014

出　　处：《中华儿科杂志》2007年第6期450-454,共5页Chinese Journal of Pediatrics

摘　　要：目的建立抗生素所致肠道菌群失调小鼠模型,在此模型上用烟曲霉菌变应原滴鼻激发,探讨变应性气道反应和肠道菌群失调的关系。方法 60只雌性 BALB/c 小鼠分为6组,每组10只。①抗生素1组:口服头孢哌酮7 d,第7天给予50μl白色念珠菌1次;②对照1组:1～7 d 给予等量生理盐水代替头孢哌酮和白色念珠菌(①和②组于第8天断颈后取盲肠内容物做细菌和真菌培养计数);③抗生素加激发组:前7天处理同抗生素1组,9、16 d 经鼻给予烟曲霉菌变应原50μl;④抗生素2组:前7天处理同抗生素1组,9、16 d 经鼻给予50μl生理盐水;⑤激发组:前7天处理同对照1组,9、16 d 经鼻给予烟曲霉菌变应原50μl;⑥对照2组:前7天处理同对照1组,9、16 d 经鼻给予50μl生理盐水(③～⑥组于第19天检测肺部气道变应性)。结果①抗生素1组小鼠肠道内肠杆菌、肠球菌、双歧杆菌、乳酸杆菌减少,白色念珠菌增加,伴体重减少,粪便含水量增加,表明肠道菌群失调。②抗生素加激发组和激发组小鼠支气管肺泡灌洗液(BALF)中细胞总数、淋巴细胞、中性粒细胞和嗜酸性粒细胞增加,尤以抗生素加激发组小鼠更为明显。③抗生素加激发组的 BALF 中 IL-4(45.35±2.36)pg/ml 较对照2组(35.32±2.53)pg/ml 增加,GATA-3转录因子 mRNA 表达水平(0.569±0.023)比对照2组(0.410±0.020)高,T-bet/GATA-3比值(0.578±0.021)较对照2组(0.804±0.035)降低。结论抗生素致肠道菌群失调小鼠经过烟曲霉菌变应原气道激发,可致 Th2优势反应的气道变应性,提示抗生素致肠道菌群失调是诱发哮喘等变应性疾病发生的危险因素。Objective Over the past several decades, there has been a significant increase in allergy and asthma in the world, which correlates with alterations in microflora and widespread use of antibiotics. The authors have developed a mouse model of antibiotics-induced microbiota disruption. In that model, mice were challenged by intranasal exposure to Aspergillusfumigatus allergens to explore the relation of allergic airway response and intestinal microflora disruption. Methods Sixty female BALB/c mice were divided at random into 6 groups with 10 mice in each. （1） First antibiotic therapy group： the mice were given oral cefoperazone for 7 days, on day 7, mice were inoculated with Candida alb/cans（ 109/ml, 50 μl） orally. （2） First control group： the mice were treated as first antibiotic therapy group, but cefoporazone and Candida albicans were replaced by saline. The mice in groups （1） and （2） were sacrificed on day 8, and cecal contents were collected for quantitative analysis of the intestinal bacterial flora. （3） Antibiotic therapy and challenge group： the mice were treated as the first antibiotic therapy group, then challenged （day 9 and 16） by intransal exposure to Aspergillus fumigatus allergen. （4） Second antibiotic therapy group： the mice were treated as the first antibiotic therapy group, then challenged （day 9 and 16） by intransal exposure to saline. （5）Chanenge group： the mice were treated as the first control group, then challenged （day 9 and 16） by intransal exposure to Aspergillus fumigatus allergen. （6） Second control group： the mice were treated as the first control group, then challenged （day 9 and 16） by intransal exposure to saline. The mice in （3）- （6） group were killed for analysis of allergic airway response on day 19. Results The quantity of Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacilus in first antibiotic therapy group was significantly lower than that in the first control group, the quantity of Candida a

关 键 词：抗生作用 呼吸超敏反应 哮喘 抗菌药 曲霉菌 烟 

分 类 号：R562.25[医药卫生—呼吸系统]