JP2017074077A - 非アルコール性脂肪肝治療用組成物、非アルコール性脂肪肝の治療剤の候補物質のスクリーニング方法及びdnaチップ - Google Patents
非アルコール性脂肪肝治療用組成物、非アルコール性脂肪肝の治療剤の候補物質のスクリーニング方法及びdnaチップ Download PDFInfo
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Abstract
Description
上記接触工程の後に、β−クリプトキサンチンの投与により発現が抑制される遺伝子の発現を検出する検出工程と、
β−クリプトキサンチンの投与により発現が抑制される遺伝子の発現を抑制した候補物質を選択する選択工程と、を含む非アルコール性脂肪肝の治療剤の候補物質のスクリーニング方法。
本発明の治療用組成物は、β−クリプトキサンチンを含む。β−クリプトキサンチンは、ウンシュウミカン等の柑橘類等に多く含まれるカロテノイドであり、プロビタミンAとしての特性を備えており、抗酸化性、抗癌作用、歯周病の予防及び改善等の作用を有することが知られている(例えば、Biol,Pharm.Bull,1995:18(2):227、特許公開2007−246448号公報等を参照)。
本発明者は、非アルコール性脂肪肝(高脂肪食や高コレステロール食の摂取によって生じた脂肪肝及び脂肪肝炎等)、及び、本発明の治療用組成物によって非アルコール性脂肪肝が治療された後の肝臓等における遺伝子発現プロファイルを、DNAマイクロアレイを用いて解析した。その結果、非アルコール性脂肪肝において特徴的に発現する遺伝子を特定した(表1参照)。従って、候補物質による、該遺伝子の発現の有無や発現量を検討し、所望の効果を奏する候補物質を選択することにより、本発明の治療用組成物と同様に非アルコール性脂肪肝を治療できる治療剤の候補物質をスクリーニングできる。
(1)高脂肪高コレステロール食によって脂肪肝炎を誘導したマウス(図1中「CL」)、(2)高脂肪高コレステロール食によって脂肪肝炎を誘導した後に、β−クリプトキサンチンを摂取させたマウス(図1中「CL+CX」)のそれぞれの肝臓組織の染色を行った。なお、(2)のマウスには、β−クリプトキサンチン量が0.003質量%である試料を84日間にわたって摂食させた。
(A)Hematoxylin Eosin染色(図1中「H&E」):該染色により、細胞核、細胞質等が染色される。脂肪は染色されず、白い部分として残る。
(B)Azan染色(図1中「Azan」):該染色により、線維化された部分が染色される。
(C)Sirius Red染色(図1中「Sirius Red」):該染色により、線維化された部分が染色される。
(D)αSMA染色(図1中「αSMA」):該染色により、活性化された星細胞を染色する。星細胞の活性化は、肝臓中に炎症反応が生じさせ、コラーゲンの過剰産生をもたらして肝臓中に沈着させる。
(E)F4/80染色(図1中「F4/80」):該染色により、活性化されたクッパー細胞を染色する。クッパー細胞の活性化は、肝臓中に炎症反応が生じていることを示す。
(1)正常肝を有するマウス(図2中「コントロール」)、(2)高脂肪高コレステロール食によって脂肪肝炎を誘導したマウス(図2中「脂肪肝炎」)、(3)高脂肪高コレステロール食によって脂肪肝炎を誘導した後に、β−クリプトキサンチンを摂取させたマウス(図2中「脂肪肝炎+β−クリプトキサンチン」)のそれぞれの肝臓組織中の遺伝子発現を、DNAチップを用いて検討した。なお、(3)のマウスには、β−クリプトキサンチン量が0.003質量%である試料を84日間にわたって摂食させた。
Claims (5)
- 少なくとも1つの候補物質と、培養肝細胞とを接触させる接触工程と、
前記接触工程の後に、β−クリプトキサンチンの投与により発現が抑制される遺伝子の発現を検出する検出工程と、
β−クリプトキサンチンの投与により発現が抑制される遺伝子の発現を抑制した候補物質を選択する選択工程と、を含む非アルコール性脂肪肝の治療剤の候補物質のスクリーニング方法。 - 前記β−クリプトキサンチンの投与により発現が抑制される遺伝子がC1QB、CD52、CD68、CD74、COL1A1、CYBA、CD64、HLA−DQA1、HLA−DQA2、HLA−DQB1、HLA−DQB2、HLA−DRB1、HLA−DRB5、LYZのうちのいずれか1つ以上である請求項1に記載のスクリーニング方法。
- 前記非アルコール性脂肪肝が非アルコール性脂肪肝炎である請求項2に記載のスクリーニング方法。
- C1QB、CD52、CD68、CD74、COL1A1、CYBA、CD64、HLA−DQA1、HLA−DQA2、HLA−DQB1、HLA−DQB2、HLA−DRB1、HLA−DRB5、LYZのうちのいずれか2つ以上のDNAを検出可能なオリゴヌクレオチドプローブを備えるDNAチップ。
- 配列番号1〜30記載の配列又はその相補配列を有するオリゴヌクレオチドプローブを2種以上備えるDNAチップ。
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WO2022025387A1 (ko) * | 2020-07-28 | 2022-02-03 | 고려대학교 산학협력단 | Microrna조합을 이용한 비알코올 지방간염 진단용 바이오마커 |
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KR102328770B1 (ko) * | 2020-06-01 | 2021-11-19 | 고려대학교 산학협력단 | 비알코올 지방간염 진단용 바이오마커 miRNA-4449 |
WO2022025387A1 (ko) * | 2020-07-28 | 2022-02-03 | 고려대학교 산학협력단 | Microrna조합을 이용한 비알코올 지방간염 진단용 바이오마커 |
KR102360963B1 (ko) | 2020-07-28 | 2022-02-09 | 고려대학교 산학협력단 | microRNA조합을 이용한 비알코올 지방간염 진단용 바이오마커 |
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