{"created":"2021-12-08T06:06:56.752427+00:00","id":2000123,"links":{},"metadata":{"_buckets":{"deposit":"db62f649-ef31-4208-ae76-4d6e51fa7ca5"},"_deposit":{"id":"2000123","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000123"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000123","sets":["453:456","471:537:538:1638942799896"]},"author_link":[],"item_1627361970403":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-03","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"89","bibliographicPageStart":"79","bibliographicVolumeNumber":"134","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"ja"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"近年，細胞療法の研究が盛んに行われているが，その治療メカニズムは多面的と考えられている．著者らのグループらは，ミクログリアや末梢血単核球(PBMC)に軽度の脳梗塞類似の刺激，すなわち低酸素低糖刺激(OGD)により，これらの細胞が保護的な極性に変化することを見出した．また，OGD刺激を施したPBMC(OGD-PBMC)を，脳梗塞7日後のラットに，頸動脈投与することで，機能予後を著明に回復させることを報告した．しかし，OGD-PBMCが血液脳関門(BBB)を透過し，脳組織保護的に作用する機序が明確ではなかった．今回OGD-PBMCの，BBB透過と脳組織保護作用獲得機序の分子機構について検討した．ラット末梢血からPBMCを遠心分離し，18時間OGD刺激(OGD-PBMC)，あるいは18時間通常培養(Normoxic-PBMC)を行った．培養馴化培地または細胞溶解物を用い，ウエスタンブロッティングによる半定量評価にて，保護作用獲得機序を解明するために次の要因について評価した．血管新生，軸索進展を誘導する血管内皮増殖因子(VEGF)，抗炎症性サイトカインであるトランスフォーミング増殖因子(TGF-β)，抗炎症性因子を誘導する転写因子PPARγ，炎症性PBMCの細胞表面マーカーであるiNOS，さらに組織保護的PBMCの細胞表面マーカーであるCD206．脳内移行性獲得の評価のため，細胞接着因子であるα4β1—インテグリン(VLA4)について，PBMCの免疫染色を行った．また，単球化学誘引物質タンパク質—1(MCP1)についてウエスタンブロッティングによる半定量評価を行った．各々の細胞の培養馴化培地のVEGFの分泌は，OGD-PBMCでは認められたのに対し，Normoxic-PBMCでは認められなかった．またTGF-βの分泌は，OGD-PBMCではNormoxic PBMCと比較して，亢進していた(p=0.044)．各々の細胞溶解物では，PPARγは，OGD-PBMCで発現が増加していた(p=0.001)．炎症性の単球／マクロファージに対する，抗炎症性の保護的な単球／マクロファージの極性化を反映しているCD206/iNOS比は，Normoxic PBMCと比してOGD-PBMCでは6倍に増加していた(p=0.023)．VLA4陽性PBMC細胞数は，Normoxic PBMCと比し，OGD-PBMCでは増加していた(p<0.001)．また，MCP-1はNormoxic-PBMCに比しOGD-PBMCで分泌が亢進していた(p=0.006)．以上からOGD-PBMCでは，PPARγ上昇により細胞保護的な特性をもつ種々の成長因子，サイトカインの分泌を亢進することを示した．また，OGD-PBMCの脳内への細胞移行の促進は，細胞接着因子VLA-4の発現増加及び走化性因子MCP-1の分泌の亢進を介している可能性が示唆された．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会","subitem_publisher_language":"ja"}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0029-0440","subitem_source_identifier_type":"PISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"二宮, 格","creatorNameLang":"ja"},{"creatorName":"Ninomiya, Itaru","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2021-12-08"}],"displaytype":"detail","filename":"134(3)_79-89.pdf","filesize":[{"value":"3.69MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000123/files/134(3)_79-89.pdf"},"version_id":"71552d6c-0e85-4c18-9b7c-7b16d0ce11ad"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"脳梗塞","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"細胞移植療法","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"末梢血単核球","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"低酸素低糖刺激","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"PPARγ","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"VLA-4","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"MCP-1","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental 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