Understanding placental dysfunction and developing treatment strategies from AQP1 in hypertensive disorder of pregnancy

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20957
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: University of Toyama
• Principal Investigator: Muroi Shin-ichi 富山大学, 和漢医薬学総合研究所, 研究員 (70965714)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 妊娠高血圧症候群 / アクアポリン / 和漢薬 / レニンアンジオテンシン系 / アポトーシス / サイトカイン

Outline of Final Research Achievements

Hypertensive disorders of pregnancy (HDP) is the most common medical problem encountered during pregnancy. Dysfunction of the placenta is thought to be one of the causes of HDP, but detailed mechanism is still unknown. In this study, we investigated the mechanism of decreased AQP1 expression in the placenta of HDP model mice and explored WAKANYAKU that can pharmacologically modulate AQP1 expression. Analysis of placental tissue at various stages of pregnancy suggested that the decrease in AQP1 caused by inflammatory cytokines may increase the fragility of placental tissue, resulting in placental tissue dysfunction. In addition, several herbal extracts and their components inhibit the RAA system, which is overactivated in HDP. These results might to be an useful data for establishing new treatment methods for HDP.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

深刻な出生率の低下の背景には，社会が妊娠の機会を奪っているだけでなく妊娠高血圧症候群などの妊娠時疾患の存在も重要であるにも関わらず，有効な治療法の確立および詳細な病態形成メカニズムの解明がなされていない．本研究では妊娠高血圧症候群の病態形成メカニズムのうち，胎盤組織傷害におけるAQP1発現減少のメカニズムをモデルマウスを用いて明らかにした．さらに，妊娠高血圧症候群の新規治療薬を使用経験の豊富な和漢薬から探索することで，妊娠への影響が少ない可能性のある候補化合物を見出すことができた．本研究の成果は妊娠高血圧症候群の治療満足度の向上につながる有用な基礎データであると考えられる．