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大学・研究所にある論文を検索できる 「ポリグリコール酸シートと塩基性線維芽細胞増殖因子を用いた内視鏡的粘膜下層剥離術後の食道狭窄に対する新規予防法の開発」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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ポリグリコール酸シートと塩基性線維芽細胞増殖因子を用いた内視鏡的粘膜下層剥離術後の食道狭窄に対する新規予防法の開発

西村, 友佑 北海道大学

2023.12.25

概要

【背景と目的】
内視鏡的粘膜下層剥離術(ESD;endoscopic submucosal dissection)は表在型食道癌
に対する治療の第一選択として広く浸透した手技である。臓器を温存できることが最
大の利点であるが、周在性の大きい切除、特に 3/4 周性以上の切除では ESD 後の食道
狭窄を高確率で引き起こし、複数回の食道バルーン拡張術を要するなど患者の生活の
質(QOL;quality of life)を著しく低下させる。現在実地臨床の予防法として、ステ
ロイドの全身投与や局所注射が主に用いられているが、その有害事象が問題視されて
おり、さらに全周性の切除に対してはステロイドの有用性が認められていない。
また、狭窄予防法としてポリグリコール酸(PGA;polyglycolic acid)からなるシー
トを用いている施設もあるが、単独での狭窄予防効果は不十分で、十分な効果を得る
にはステロイドとの併用を要するのが現状である。
一方、線維芽細胞促進因子(FGFs;fibroblast growth factors)は創傷治癒を促進す
る重要な因子として知られており、特に塩基性線維芽細胞増殖因子(bFGF;basic FGF)
は医薬品として製品化され褥瘡や皮膚潰瘍の治療に用いられているが、消化管に用い
た報告はない。
今回、我々はブタ全周性食道 ESD モデルに対し PGA シートと bFGF を併用すること
による、ステロイド投与を要さない新規の狭窄予防法の開発を本研究の目的とした。
【対象と方法】
本研究は北海道大学の動物実験委員会の承認を得て行った。20-25 kg のメス三元交
配ブタを用いて、長軸方向 3 cm の全周性食道 ESD モデルを作成した。創部に対し
bFGF を浸した PGA シートを貼付した群を PGA+bFGF 群、PGA シートを単独で貼付した群
を PGA 群、何も治療を施さない群をコントロール群とした。各群はそれぞれ 3 頭ずつ
とし、ESD 後 22 日目に安楽死させ食道を摘出し狭窄率を評価した。摘出した標本に
対してはヘマトキシリン・エオジン(HE;hematoxylin eosin)染色の他、免疫染色(α
SMA、Calponin-1、CD107a、MPO、Elastica Masson)を行い、創部における炎症反応や線
維化の状態について病理学的な検討を行った。各項目は対応のない Student の t 検定
および両側検定を用いて比較した。
また、in vitro の実験としてラット由来歯根膜幹細胞を培養したコラーゲンコート
ディッシュに TGF-β1 や FGF-2 を添加し、細胞分化の状態を観察した。さらにα
SMA、Calponin-1、COL 1a1、COL 1a2 遺伝子の発現について RT-qPCR を行い、発現量を
評価した。 ...

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