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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 To establish a mouse model of intestinal flora dysbiosis induced by antibiotics. In this model, intranasal challenge with Aspergillus fumigatus allergen was conducted to investigate the relationship between allergic airway response and intestinal flora. Methods Sixty female BALB / c mice were divided into six groups of 10. ① antibiotics group 1: oral cefoperazone 7 d, giving 50μl of Candida albicans on the 7th day; ②control group 1: the same amount of saline was given on days 1-7 instead of cefoperazone and Candida albicans (① and ② groups On the 8th day, the cecum contents were removed and counted for bacterial and fungal culture. ③ Antibiotics and challenge groups: 1 group was treated with antibiotics in the first 7 days, and 50μl of Aspergillus fumigatus allergen Antibiotics 2 groups: treated with antibiotics in the first 7 days, and administered with 50μl of saline on the 9th and 16th days. ⑤ Excitation group: the first seven days were treated with the control group 1, and the A. fumigatus allergen The control group 2: the first 7 days treatment with the control group 1, 9,16 d nasal administration of 50μl saline (③ ~ ⑥ group on the 19th day detection of airway airway allergy). Results ① In the antibiotic group 1, enterobacter enterococci, enterococci, bifidobacteria and lactobacilli were decreased in the intestinal tract of mice. The number of Candida albicans increased, body weight decreased and water content increased. (2) The total number of cells, lymphocytes, neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF) increased significantly in the group of antibiotics plus challenge and challenge, especially in the mice treated with antibiotics plus challenge group. ③ The level of IL-4 (45.35 ± 2.36) pg / ml in BALF of the antibiotic plus challenge group was significantly higher than that of the control group 2 (35.32 ± 2.53) pg / ml, and the mRNA expression level of GATA-3 transcription factor (0.569 ± 0.023) (0.410 ± 0.020), and the ratio of T-bet / GATA-3 (0.578 ± 0.021) was lower than that of control group 2 (0.804 ± 0.035). Conclusion Antibiotic-induced intestinal flora dysfunction in mice airway induced by Aspergillus fumigatus allergen can lead to allergic Th2 predominant airway allergy, suggesting that antibiotic-induced intestinal flora imbalance is the induction of allergic diseases such as asthma Risk factors.