The Pathogenesis Of Emphysema Mouse SP-C-rtTA;（tetO）₇-Cre;pMES-Noggin

Pulmonary emphysema,a chronic respiratory disease which seriously threatens physical and emotional health of patients,is characterized by degenerate elasticity of the airway at the terminal bronchioles,enlargeent of the lung volume and destruction of the airway wall.Although becoming severe public health issue around the globe,the pathogenesis of pulmonary emphysema has remained ambiguous and there are no specific medicines and treatments.Therefore,the research of pathogenic mechanism is of great significance for the exploition of clinical drugs and the perfection of the therapies.All the time,the construction of animal model is one of the most effective methods to study pathogenesis,so we established the genetically modified mice:SP-C-rtTA;(tetO)7-Cre;pMES-Noggin with forced expression of Noggin in lung type II epithelial cells Indu? ced by Dox.It found the severe phenotype of pulmonary emphysema when the mice was raised with Dox for 7 days,fed without the medicine until 1M,3M,6M.To explored the earliest onset of pulmonary emphysema in transgenic mice,we harvested the mice lung at the hours of 12h,24h and 48h after Dox.And discovered that mice appeared comprehensive pulmonary emphysema at the 48h after Dox.Until 72h,the emphysema alveolus has further enlarged along with the rupture of a large number of alveolar septum.Pathological examination found that apoptosis is active in alveolar epithelium 12h after Dox,transmission electron microscopy images also demonstrated serious damage of the ultrastructure in lung type Ⅱ epithelial cells.However,after 72h of Dox,the expression of neutrophil elastase is extremely enhanced,elastin was degradative and tissue inflammation.It indicates that the inflammation may result from large number of apoptotic alveolar epithelial cells,the outbreak of tissue inflammation cause a large release of elastase which results in the extracellular matrix protein are hydroyzed.These symptoms eventually result in the excessive expansion of alveolar and lead to pulmonary emphysema.Finally,we extracted the RNA from the distal lung tissues in littermate control and SP-C-rtTA;(tetO)7-Cre;pMES-Noggin mice.Through protein interaction network analysis,selected 11 core genes related to pulmonay emphysema,which including Serpina3m,Ptgs2,Cdkl,Fosb,Rasllla,Ccno,Kif18b,kifla,Ccl11,Atp6v0a4,Cxcl9.Tnn which is directly interaction with Noggin is associated with cell proliferation and apoptosis.This further illustrate that Overexpression of Noggin may disrupt the steady state between cell proliferation and apoptosis which triggers inflammation and imbalance between protease and antiprotease,and it ultimately leads to pulmonary emphysema.