Clarifying the mechanism of the imunosupression by anesthetics via Kv 1.3 channel

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Tohoku University
• Principal Investigator: Toyama Hiroaki 東北大学, 医学系研究科, 准教授 (00375007)
• Co-Investigator(Kenkyū-buntansha): 風間 逸郎 東北大学, 医学系研究科, 大学院非常勤講師 (60593978)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 尿管閉塞 / 慢性腎不全 / Kv1.3チャネル / 間質性腎炎 / 免疫抑制

Outline of Final Research Achievements

We compared the normal kidney tissues and kidney tissues of chronic nephritis by the histologically and immunohistologically for 3 weeks after the unilateral ureteral obstruction in rats. The longer ureteral obstruction, the more T lymphocytes and macrophages were found at the interstitium of the renal cortex. However, In the rats that were administered 200nM/mL of margatoxin intraperitoneally, less T lymphocytes and macrophages and the decrease expression of fibrosis markers were found at the interstitium of the renal cortex, which indicated that margatoxin could inhibit the infiltration of lymphocytes and fibrosis in interstitium of the renal cortex. Additionally, by the histopathological images of the renal cortex in the rat administered with margatoxin, decrease of white blood cells and inhibition of white blood cell proliferation were also indicated.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

ラットの尿管閉塞後、尿管閉塞腎と正常腎を組織学的に比較した。尿管の閉塞期間が長い程、腎臓間質にTリンパ球とマクロファージの増加を認めた。しかし、Kv1.3チャネル選択的阻害薬マルガトキシンを連日200nM/mL腹腔内投与したラットは、腎皮質間質の線維化マーカーの発現減少を認め、マルガトキシンが腎皮質間質におけるリンパ球浸潤と間質線維化を抑制することが示された。組織像ではマルガトキシン治療ラットで顕著な白血球数減少と白血球増殖抑制も認めた。リンパ球膜表面Kv1.3チャネルへの標的治療により腎間質線維化を抑制できると考えられ、慢性腎不全進行を抑制する今後の治療薬開発への一助となると考えられた。