臨床外科73巻9号

2018年09月発行

FOCUS

体内時計と外科—切除不能大腸癌肝転移に対する時間治療の応用

著者： 田中邦哉¹ 川口大輔² 国崎主税²

所属機関： ¹昭和大学藤が丘病院消化器・一般外科 ²横浜市立大学市民総合医療センター消化器病センター外科

ページ範囲：P.1140 - P.1148

はじめに
　ヒトを含めた動物では，明暗などの外的環境の周期的変化に伴い，その生体機能も周期的に変化することが知られている．このおおむね一日の周期的なリズムを概日リズムあるいはサーカディアンリズムと呼ぶ．サーカディアンリズムは24.2〜25.1時間（24.8時間）の変動リズムであり，地球の一日の周期よりやや長い．通常この差を，太陽光による光刺激によって，睡眠・覚醒の位相反応曲線を前進あるいは後退させることにより同調（synchronizationあるいはエントレインメントentrainment）させる．哺乳類におけるこれらリズムを調節する時計中枢は，視床下部の前方にある1万6千個の細胞群からなる視交叉上核に存在する．また，明暗刺激に対する同調は，松果体と網膜およびこの視交叉上核の3つが関与する．視神経交叉の上部に位置する視交叉上核は背内側部（シェル）と腹外側部（コア）とに分かれ，自発的なリズムはシェル内に蓄えられている．一方で，光刺激が網膜に入射することでコアが興奮し，シェルのリズムを再起動する．視交叉上核から発せられたリズムの信号は松果体へ伝えられ，松果体ではこの情報に応答してメラトニンを分泌する．メラトニンはセロトニンから松果体で生成され，光刺激入射後14〜16時間で分泌を開始し，その分泌は夜間に高く昼間に低い．この視交叉上核は，哺乳類の身体の中では親時計（主要時計）の役目を果たしており，これ以外に親時計に支配された子時計（末梢時計）が存在し，連携してリズムを形成している．末梢時計は自身では長時間リズムを作れないため，普段は主要時計の支配下にあるが，状況に応じて独自に動く柔軟性を備えている．肝臓内にある末梢時計は食事の時刻によりリズムが変わることが知られている．これら末梢時計は肝臓に加えて，心臓，腎臓，血管，皮膚，口腔粘膜，末梢血単核球などに存在する．
　近年，これら生体リズムと悪性疾患との関連が明らかになってきており，リズムを応用した治療（時間治療）が悪性疾患治療に応用されつつある．本稿では時間治療を応用した癌治療を，筆者が行っている大腸癌肝転移治療を中心に紹介する．

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