@techreport{oai:mie-u.repo.nii.ac.jp:00008138, author = {小林, 哲 and KOBAYASHI, TETSU and Esteban, Gabazza and 田口, 修 and TAGUCHI, OSAMU}, month = {May}, note = {application/pdf, siRNAは難治性疾患に対する根本的治療法の開発ツールとして注目されている。我々は、ブレオマイシン肺線維症マウスモデルに対して種々のsiRNAを作成し、経気道的に投与し、その病態抑制に成功した。さらにヒト化肺線維症マウスモデルの作成に成功し、それに対して、ヒトに対するsiRNAを作成し、経気道的に投与しその病態制御をすることが出来た。今後、本法を用いた創薬に期待できる結果となった。, SiRNA has been the focus of attention for its potential application for the development of new drugs.To evaluate the effect of intratracheal administration of siRNAs in murine disease models. Firstly, bleomycin was used for induction of lung fibrosis. After confirming the effectiveness of siRNA effect in vitro, siRNAs for several targets including TGF-beta1 were intratracheally administered by inhalation. Mice treated with scrambled siRNA or vehicle were used as controls. We generated a novel model of human TGF-beta1 transgenic mouse that spontaneously develops pulmonary fibrosis. Intrapulmonary delivery of aerosolized siRNAs of TGF-beta1 significantly inhibited bleomycin-induced pulmonary fibrosis. In addition, aerosolized siRNAs against human TGF-beta1 also inhibited spontaneous pulmonary fibrosis.These results suggest that intratracheal instillation of RNAi agents may be useful for the therapy of airway remodeling., 2010年度~2012年度科学研究費補助金(基盤研究(C))研究成果報告書, 22590859}, title = {siRNAによる気道リモデリング制御方法の検討及び創薬の可能性の検討}, year = {2013} }