| Project/Area Number |
18K08137
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Tamada Tsutomu 東北大学, 医学系研究科, 准教授 (80396473)
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| Co-Investigator(Kenkyū-buntansha) |
奈良 正之 東北大学, 医学系研究科, 非常勤講師 (70374999)
村上 康司 東北大学, 大学病院, 助教 (70633725)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 気道分泌 / COPD増悪 / 気道粘膜防御機構 / CFTR / HCO3- / 酸性 / COPD / LABA / 気道粘膜下腺 / 増悪 / 新鮮気道分泌液 / 過分泌 / 粘液線毛輸送能 / 呼吸器内科 / 気道粘膜防御 |
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| Outline of Final Research Achievements |
An acquired dysregulation of airway secretion is likely involved in the pathophysiology of COPD. However, limited data are available concerning the complementary additive effects of bronchodilators on airway secretion. ACh 100 nM induced a gradual increase in the amount of gland secretion in swine tracheal membrane. LPS accelerated the ACh-induced secretory responses up to around 3-fold and significantly lowered the pH level. LABAs restored the LPS-induced changes in both the hypersecretion and acidification. Two different inhibitors for CFTR abolished the LABA-mediated pH normalization. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, LABA did not restore the LPS-induced decrease in CFTR expression. These findings suggest that the activation of cAMP-dependent HCO3- secretion through CFTR would be partly involved in the LABA-mediated pH normalization in gland secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
COPD増悪頻回例は呼吸機能の低下が著しく、症状が強く、生活の質が低下し、予後が悪化する。COPD増悪にかかる医療費は年間約6,000億円とCOPD全体の75%と試算される。COPD増悪抑制は疾患予後改善だけでなく医療資源の有効活用・医療費抑制のためにも急務である。本研究では、ヒト同様の構造的および機能的特徴を有するブタ気道からの新鮮分泌液の観察と解析に成功し、長時間作用性気管支拡張薬が気道分泌液を正常化し気道粘膜防御機構脆弱性の改善効果をもたらす可能性を初めて示した。本研究成果は、ウイルスや細菌感染など気道易感染性に伴って生じるCOPD増悪抑制のための新規治療法開発への基礎を提供する。
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