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新生期母婴分离对成年哮喘小鼠短链脂肪酸及气道炎症的影响

The effect of neonatal maternal separation on short-chain fatty acids and airway inflammation in adult asthma mice.

作者信息

Qian L, Lu L, Huang L, Wen Q, Xie J, Jin W, Li H, Jiang L

机构信息

Department of Pediatrics, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China; Teaching and Research Section of Pediatrics, Medical College, Southeast University, Nanjing, Jiangsu 210009, China.

Department of Neonatology, Suzhou Municipal Hospital, Suzhou, Jiangsu 210002, China.

出版信息

Allergol Immunopathol (Madr). 2019 Jan-Feb;47(1):2-11. doi: 10.1016/j.aller.2018.05.004. Epub 2018 Nov 17.

Abstract

BACKGROUND

To investigate neonatal maternal separation (NMS) effects on airway inflammation of asthma and potential mechanism using a mouse model.

METHODS

80 Balb/c neonatal male mice were randomly assigned to NMS and non-NMS groups. Feces were collected on PND21, 28, 35 and 42 to analyze microbiota and short-chain fatty acids (SCFAs). Non-NMS group were then divided into control (group A) and asthma groups (group B), while NMS group was assigned to NMS+asthma (group C) and NMS+SCFAs+asthma groups (group D). Inflammatory cells and eosinophils (EOS) in bronchoalveolar lavage fluid (BALF) were assessed. Pathological changes and cytokines in lung tissue were observed. Protein expression of Occludin and E-cadherin in airway epithelial was examined.

RESULTS

The number of S', diversity index H' and dominance index D', as well as content butyric acid in NMS group C were significantly lower than non-NMS group B (p<0.05). Mice in group C had a higher level of inflammatory cells and EOS compared with group A, B and D. EOS moderate infiltration was found in mice of group B, C and D. Mice in group C had significantly higher levels of cytokines and showed slightly increased bronchial epithelium goblet cells and a small amount of visceral secretions. Occludin and E-cadherin expression in lung in B, C and D groups was depressed, and protein level in group C was significantly lower than group B and D.

CONCLUSIONS

NMS is associated with exacerbated inflammation of adult asthma by changing intestinal microflora resulting in butanoic acid decline and airway epithelial barrier damage.

摘要

背景

利用小鼠模型研究新生鼠母婴分离(NMS)对哮喘气道炎症的影响及其潜在机制。

方法

将80只Balb/c新生雄性小鼠随机分为NMS组和非NMS组。在出生后第21、28、35和42天收集粪便,分析微生物群和短链脂肪酸(SCFAs)。然后将非NMS组分为对照组(A组)和哮喘组(B组),而NMS组分为NMS+哮喘组(C组)和NMS+SCFAs+哮喘组(D组)。评估支气管肺泡灌洗液(BALF)中的炎症细胞和嗜酸性粒细胞(EOS)。观察肺组织的病理变化和细胞因子。检测气道上皮中紧密连接蛋白(Occludin)和E-钙黏蛋白(E-cadherin)的蛋白表达。

结果

NMS组C的S'数量、多样性指数H'和优势度指数D'以及丁酸含量均显著低于非NMS组B(p<0.05)。与A、B和D组相比,C组小鼠的炎症细胞和EOS水平更高。在B、C和D组小鼠中发现EOS中度浸润。C组小鼠的细胞因子水平显著更高,支气管上皮杯状细胞略有增加,并有少量内脏分泌物。B、C和D组肺组织中Occludin和E-cadherin表达降低,C组蛋白水平显著低于B组和D组。

结论

NMS通过改变肠道微生物群导致丁酸减少和气道上皮屏障损伤,与成年哮喘炎症加剧有关。

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