The construction of combination therapy of exercise and medication on DCM model mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K17686
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Juntendo University
• Principal Investigator: Sugihara Masami 順天堂大学, 医学部, 助教 (80648163)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 運動療法 / 拡張型心筋症 / 心不全 / 心室性不整脈

Outline of Final Research Achievements

Dilated cardiomyopathy (DCM) is one of major causes of heart failure (HF). Today, exercise is regarded as one of therapies for HF. However, the effects of exercise on patients with DCM have not been established. A knock-in mouse model of human inherited DCM is useful for investigating inherited DCM. Homozygous mice were divided into four groups based on the administration of angiotensin receptor antagonist (ARB) and voluntary exercise: without drug or exercise control, oral administration of ARB, daily exercise and both of ARB and exercise (BOTH). The all groups started medication and running at 1 month of age. At the 2.5 months of age, mice were sacrificed after an investigation with echocardiography. BOTH group was significantly improved in ejection fraction. On the other hand, exercise group showed less E/e’ than the other groups, The wights of soleus muscles in the exercise group were more increased than BOTH group and were thought to be associated with diastolic function.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

研究代表者は、循環器内科医としての診療の中でDCMでも適切な運動の効果が推測された症例を経験している。しかし、多くのDCM患者においては、進行してから受診する例が多く運動療法を試みる機会を逸しやすい、易不整脈性のため運動プロトコルが決めにくい、環境や遺伝的要因、薬物介入によるバラつきが大きい、という点で評価が難しい状況が続いている。
本研究では、遺伝的背景の均一なモデル動物を解析できるので効果を定量的に検討できる。また、近年発達している遺伝子診断と合わせ、病態進行に合わせた運動療法のプロトコルの確立に寄与することが期待できる。