Novel fetal treatment for congenital diaphragmatic hernia using nitrofen induced rat model

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20343
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Kindai University (2018); Osaka University (2016-2017)
• Principal Investigator: UMEDA Satoshi 近畿大学, 医学部附属病院, 診療講師 (60715176)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 先天性横隔膜ヘルニア / 肺低形成 / 胎児治療 / プロスタサイクリンアゴニスト / 徐放性製剤

Outline of Final Research Achievements

On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the number of Ttf-1-positive cells and the capillary density were 1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of VEGF in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、先天性横隔膜ヘルニアに伴う肺低形成に対して母体に徐放性製剤を投与することで、児の肺高血圧の治療および低形成肺の成長促進を確認した点に特色がある。これまで、肺低形成の胎児治療としてプロスタサイクリンやその受容体アゴニスト製剤によって胎児治療を試みたという報告はなく、またDDSの投与によって胎児治療を行ったという研究もないため、胎児治療法としても極めて独創的である。本研究成果は、今後先天性横隔膜ヘルニアにおける肺低形成に対する胎児治療の臨床応用に直結できることが期待され、大変意義深いと考えられる。