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外傷後敗血症病態に関与する好中球フェノタイプの研究

水柿, 明日美 北海道大学

2023.09.25

概要

【背景と目的】重症外傷による死亡は、受傷後からの時期によって 3 つに分け
ることができる。すなわち、治療介入の余地がない超急性期の死と、医学・医
療の進歩によって死亡率が改善してきた急性期の死、そして現時点では支持的
療法が中心で根本的治療方法が確立されていない亜急性期~慢性期の死である。
救命率の比較的低い外傷急性期を乗り越えたにもかかわらずその後の亜急性期
~慢性期に命を落とす原因としては、手術侵襲や二次性に発症する感染症・敗
血症による臓器不全が考えられているが、その機序としては免疫恒常性の破綻
が知られている。好中球は、自然免疫の中核を担い、感染症の最前線で病原体
を排除する役割を持つことで広く知られてきた。しかし近年、炎症性好中球だ
けではなく、抗炎症作用を持つ好中球など様々な機能を有する好中球フェノタ
イプの存在が指摘されている。腫瘍性疾患や自己免疫性疾患、アレルギー性疾
患を中心としてさまざまな病態に好中球フェノタイプが関与している可能性が
示唆されている。外傷後敗血症病態にも好中球フェノタイプの偏在が関与して
いることが報告されているが、その全容は依然として明らかにされていない。
外傷後敗血症病態における好中球フェノタイプの関与を明らかにし予後と関連
する因子について検討する目的で本研究を行った。本研究では外傷後敗血症モ
デルマウスを用い、生存率や腹水生菌数の検討、病理組織学的解析を行った。
さらに、同モデルマウスの血液および腹水中サイトカイン測定や好中球フェノ
タイプの解明を目的としたマスサイトメトリーによる免疫学的解析を行った。
【材料と方法】週齢 7-8 の雄の ICR マウスを用いて外傷後敗血症マウスモデル
を作製した。外傷として 25%3 度熱傷もしくはコントロールとして Sham を施
し、受傷 24 時間後に盲腸結紮穿孔(cecal ligation and puncture: CLP)を行うこと
によって敗血症を引き起こし、熱傷を施した Burn/CLP モデルと、Sham を施し
た Sham/CLP モデルを作製した。CLP 後 14 日間生存率、CLP 翌日の腹水生菌数、
CLP 翌日の脾臓、肝臓、腎臓、肺組織の病理組織学的所見を両群間で比較した。
さらに両群の血清および腹水のサイトカイン測定と、血液中および腹水中の好
中球、単球・マクロファージに的を絞ったマスサイトメトリーによって免疫学
的解析を行った。
【結果】Burn/CLP 群は Sham/CLP 群と比較し有意に生存率が低かった。腹水生
菌数測定においては Burn/CLP 群と Sham/CLP 群の間に有意な差を見出すことが
できなかったが、病理組織学的検査では Sham/CLP 群と比較して Burn/CLP 群で
は脾臓組織中のマクロファージが少なく、肝臓、腎臓、肺の組織では Burn/CLP
群で Sham/CLP 群よりも進行した臓器障害が見られた。 ...

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