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ID 110054
タイトル別表記
ホルボール12-ミリスタート 13-アセタート分化誘導による巨核球系細胞を用いた血小板機能に対する各種薬剤効果の評価
Effects of various drugs on platelet functions
著者
多田, 智紀 徳島大学大学院保健科学教育部(保健学専攻)
Oboshi, Wataru Kagawa Prefectural University of Health Sciences
キーワード
platelets
intracellular Ca2+ concentration ([Ca2+]i)
aspirin
cilostazol
ibuprofen
sodium valproate
資料タイプ
学位論文
抄録
Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions.
Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions.
Materials and methods: Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs.
Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM) and cilostazol (5–10 µM) significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM) and sodium valproate (50–1,000 µg/mL) also significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca2+]i.
Conclusion: It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca2+]i is applicable to the evaluation of the effects of various drugs on platelets.
掲載誌名
Drug Design, Development and Therapy
ISSN
11778881
出版者
Dove Press
10
開始ページ
3099
終了ページ
3107
発行日
2016-09-26
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201704181007.pdf
審査要旨 : LID201704181008.pdf
論文本文 : LID201704181009.pdf
本論文は, 著者Tomoki Tadaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyrihgt© 2016 Tada et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php)
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3037号
学位記番号
甲保第30号
学位授与年月日
2017-03-23
学位名
博士(保健学)
学位授与機関
徳島大学
部局
医学系
薬学系