Metformin inhibits airway inflammation, remodeling and neovascularization in asthma mice
10.3969/j.issn.1000-4718.2017.04.003
- VernacularTitle:二甲双胍抑制慢性哮喘小鼠气道炎症、重塑及新生血管形成
- Author:
Wenxian MA
;
Haiqin GUO
;
Xinpeng HAN
;
Lingbin XU
;
Liang LIU
;
Zhichao LI
;
Changgui WU
- Keywords:
Metformin;
Airway neovascularization;
AMP-activated protein kinase;
Chronic asthma
- From:
Chinese Journal of Pathophysiology
2017;33(4):590-595
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects of metformin on airway inflammation, remodeling and neovascularization in a mouse model of chronic asthma and its possible mechanisms.METHODS: BALB/c mice were randomly divided into saline group, ovalbumin (OVA) group and OVA+metformin group, with 8 in each.At the end of OVA exposure, blood and bronchoalveolar lavage fluid (BALF) were collected for the measurement of OVA specific IgE and leukocyte counts.Lung tissue sections were stained with hematoxylin-eosin, periodic acid-Schiff and Masson's trichrome to detect inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition around the airway, respectively.Immunohistochemistry was used to evaluate the number and percentage area of new blood vessels (CD31+), and the protein level of phosphorylated AMP-activated protein kinase (p-AMPK) in the airway.RESULTS: Compared with saline group, the eosinophil percentage and OVA specific IgE in serum in OVA group were all increased obviously (P<0.01).Metformin inhibited the above increases (P<0.05).Compared with control group, a marked increase in inflammation infiltration, PAS+ cells and collage deposition in the airway mucosa in OVA group were observed.Metformin partially relieved the above changes.CD31+ vessels in the wall of bronchi showed the abundance of blood vessels observed in OVA group compared with control group, which was suppressed by the treatment with metformin (P<0.05).The protein level of p-AMPK was reduced in the lung tissue challenged with OVA as compared with control group (P<0.05), while metformin increased the protein level of p-AMPK (P<0.01).CONCLUSION: The protein level of p-AMPK in the airway in OVA group is attenuated.Metformin effectively inhibits airway inflammation, remodeling and neovascularization possibly via activating AMPK signaling pathway.