Urotensin II 수용체 길항제에 의한 혈관증식 억제 효능 및 기전

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dc.contributor.advisor정이숙-
dc.contributor.author이동길-
dc.date.accessioned2018-11-08T08:21:38Z-
dc.date.available2018-11-08T08:21:38Z-
dc.date.issued2015-02-
dc.identifier.other18896-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/13064-
dc.description학위논문(석사)--아주대학교 일반대학원 :약학,2015. 2-
dc.description.tableofcontentsAbstract i TABLE OF CONTENTS iii LIST OF FIGURES v ABBREVIATION vi Ⅰ. INTRODUCTION 1 A. Atherosclerosis 1 B. Urotensin II 1 C. Antagonists 2 D. Aims 2 Ⅱ. MATERIALS AND METHODS 3 A. Chemicals and Reagents 3 B. Cell culture 3 C. 5-bromo-2'-deoxyuridine (BrdU) incorporation 4 D. Western blotting 4 E. Measurements of reactive oxygen species (ROS) release 5 F. Mouse carotid ligation model 5 G. Hematoxylin and eosin staining 6 H. Statistical analysis 7 Ⅲ. RESULTS 8 A. Effect of KR-36676 and KR-36996 on SMC proliferation. 8 B. Inhibitory of inhibitors on UII-induced proliferation in hAoSMCs. 10 C. UII-induced ROS generation in HASMC on time course. 11 D. Effect of KR-36676 on UII-induced ROS generation in hAoSMCs. 13 E. Effect of KR-36996 on UII-induced ROS generation in hAoSMCs. 16 F. Effect of KR-36676 on UII-induced ERK activation in hAoSMCs. 18 G. Effect of KR-36996 on UII-induced ERK activation in hAoSMCs. 20 H. Effect of KR-36676 on carotid ligation-induced intimal thickening. 22 I. Effect of KR-36996 on carotid ligation-induced intimal thickening. 24 Ⅳ. DISCUSSION 26 Ⅴ. CONCLUSION 30 REFERENCES 31 국문요약 34-
dc.language.isoeng-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.titleUrotensin II 수용체 길항제에 의한 혈관증식 억제 효능 및 기전-
dc.title.alternativeLee Dong-Gil-
dc.typeThesis-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.alternativeNameLee Dong-Gil-
dc.contributor.department일반대학원 약학-
dc.date.awarded2015. 2-
dc.description.degreeMaster-
dc.identifier.localId695443-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000018896-
dc.subject.keywordUrotensin II-
dc.subject.keywordUrotensin II receptor-
dc.subject.keywordUrotensin II receptor antagonists-
dc.subject.keywordAtherosclerosis-
dc.subject.keywordERK-
dc.subject.keywordROS-
dc.subject.keywordProliferation-
dc.subject.keywordligation.-
dc.description.alternativeAbstractUrotensin-II (UII) is a vasoactive peptide that promotes vascular smooth muscle cell proliferation and is involved in the pathogenesis of atherosclerosis, restenosis and vascular remodeling. In this study, effects of KR-36676 and KR-36996, a novel selective urotensin receptor (UT) antagonist, on smooth muscle cell proliferation was examined. UII-induced proliferation of human aortic smooth muscle cells (hAoSMCs), was found to be significantly inhibited by KR-36676 and KR-36996 (1, 10, and 100 nM) in dose-dependent manner. UII-induced proliferation of hAoSMCs cells was also inhibited by U0126, an ERK1/2 inhibitor, but not by SP600125 and SB202190, inhibitors of JNK and p38 MAPK, respectively. UII increased the phosphorylation of ERK1/2, but this increase was significantly inhibited by KR-36676 and KR-36996. In addition, the UII-induced proliferation was also inhibited by trolox, a scavenger of reactive oxygen species (ROS), while the UII-induced ROS was also decreased in response to KR-36676 and KR-36996 treatment. Moreover, in a carotid artery ligation mouse model, intimal thickening was dramatically suppressed by oral treatment with KR-36676 and KR-36996 (30 mg/kg). Taken together, KR-36676 and KR-36996 attenuated UII-induced proliferation of hAoSMCs cells, at least partially, through blocking ERK1/2 activation and ROS generation.-
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Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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