201909Nakashima

研究発表を行った学会；発生研サマーリトリート 2019
2019年 8月 7日〜8日（熊本県菊池市）
タイトル； Therapeutic potential of metformin in novel murine chronic obstructive pulmonary disease (COPD) model mice with diffuse-type emphysema.
発表者；中嶋　竜之介氏
（熊本大学　大学院薬学教育部　遺伝子機能応用学分野）
要旨；
We have recently established a novel COPD mouse model, that overexpresses airway-specific epithelial Na+ channel β subunit (βENaC-Tg) (Sci Rep. 2016). Considering the trend in the therapeutic strategies for COPD that takes into account the phenotype, genotype and endotype, it is essential to compare the differences between the novel and general COPD mouse models (e.g. elastase-induced COPD model). We first developed whole lung image-based quantification for histological analysis and evaluated the histological differences. Then, we estimated the biochemical differences in both models. We demonstrated that βENaC-Tg mice exhibit diffuse-type emphysema with stable expression of inflammatory and senescence-like markers compared to elastase model (J Phamacol Sci. 2019). We next verified the therapeutic potential of metformin. In our previous study, we showed that high fat diet-induced type 2 diabetes exacerbates the COPD phenotype and advocated the concept of “pulmonary insulin resistance”. Therefore, metformin, a clinically available anti-diabetic drug that is known to improve insulin resistance, could have therapeutic potential for COPD. Administration of metformin (free-drinking water) ameliorated pulmonary emphysema and respiratory function in βENaC-Tg mice. Taken together, these data show usability of βENaC-Tg mice as a diffuse-type emphysema model and confirm the therapeutic potential of metformin for COPD.