Full metadata record

DC Field Value Language
dc.contributor.author박종수-
dc.date.accessioned2017-05-15T09:40:30Z-
dc.date.available2017-05-15T09:40:30Z-
dc.date.issued2010-12-
dc.identifier.otherMEDICINE-THESIS-2011-036-
dc.identifier.urihttp://kumel.medlib.dsmc.or.kr/handle/2015.oak/11625-
dc.description.abstractThe aim of the present study was to investigate the effects of propofol on platelet activating factor (PAF)-induced microglial activation including intracellular Ca2+ level ([Ca2+]i), cell viability, reactive oxygen species (ROS) generation and canonical transient receptor potential Ca2+ channel (TRPC) expressions, and to evaluate the inhibitory mechanisms involved. PAF was used for activation of HMO6 human microglial cells. The changes in [Ca2+]i and ROS generation were measured by using fura-2/AM and 2',7'-dichlorofluorescin diacetate, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide assay was used to evaluate cell viability. PAF-induced TRPC channel mRNA expression was analyzed by reverse transcription-polymerase chain reaction. PAF (300 nmol/L) induced an initial peak and sustained [Ca2+]i increases in human microglia. This [Ca2+]i increase was due to Ca2+ release from intracellular stores and Ca2+ influx through store-operated calcium (SOC) channel. PAF increased ROS generation whereas decreased cell viability. TRPC1 and TRPC4 mRNA expressions were significantly (p<0.05) increased after treatment of PAF. Propofol (10 μmol/L) inhibited SOC-mediated Ca2+ influx and ROS generation induced by PAF. Propofol recovered PAF-induced cell death to the levels of rotenone (mitochondrial respiratory chain inhibitor), but diphenyleneiodonium (NAPPH oxidase inhibitor) did not influence on the cell viability. Propofol significantly (p<0.05) attenuated the PAF-induced TRPC1 mRNA expression as potent as SOC channel blocker, 2-aminoethoxy diphenyl borate. These results suggest that inhibitory action mechanisms of propofol on PAF-induced microglial activation include inhibitions of SOC-mediated Ca2+ influx and mitochondrial ROS generation via a down-regulation of TRPC1 mRNA expression. 이 연구는 신경보호 작용 연구의 일환으로 혈소판활성인자(platelet activating factor, PAF)에 의해 미세아교세포가 활성화 되는 과정에서 propofol이 미치는 활성억제 효과를 검증하고 그 작용 기전을 파악하고자 하였다. 실험에 사용한 세포는 인체 유래 미세아교세포주인 HMO6세포를 이용하였다. 미세아교세포의 활성유도물질 중의 하나인 PAF (300 nmol/L)로 활성을 유도하였다. PAF에 의한 미세아교세포의 활성과 이에 대한 propofol (10 μmol/L)의 활성억제 효과를 fura-2 형광물질을 이용한 세포내 칼슘 농도 측정과 세포생존율, 활성산소 생성 및 역전사중합효소연쇄반응을 통한 canonical transient receptor potential Ca2+ channel (TRPC) 발현의 변화로 분석하였다. PAF는 미세아교세포의 세포내 칼슘저장고에서 칼슘유리를 유발시키고 store-operated calcium (SOC) 통로를 통한 세포 밖의 칼슘 유입을 촉진시켜 세포내 칼슘 농도를 증가시켰다. PAF는 활성산소의 생성을 증가시킨 반면에 세포생존율을 저하시켰다. PAF를 처리한 미세아교세포에서는 TRPC1 및 TRPC4 mRNA 발현이 유의하게(p<0.05) 증가되었다. Propofol은 PAF에 의해 유도된 SOC를 통한 칼슘 유입과 활성산소 생성을 억제하였다. 또한 propofol은 PAF에 의해 억제되었던 세포생존율을 회복시켰으며, TRPC1 mRNA를 유의하게(p<0.05) 억제하였다. 이상의 결과로 보아 propofol은 PAF에 의한 TRPC1 mRNA 발현 증가를 하향 조절함으로써 SOC를 통한 칼슘의 유입과 활성산소 생성을 차단하여 미세아교세포의 활성을 억제하는 것으로 생각된다.-
dc.description.statementofresponsibilityopen-
dc.titleEffects of Propofol on Platelet Activating Factor-Induced Microglial Activation-
dc.title.alternative혈소판활성인자에 의해 유도된 미세아교세포 활성에 대한 Propofol의 영향-
dc.typeThesis-
dc.description.degree박사-
dc.date.awarded2011-02-
dc.identifier.urlhttp://dcollection.kmu.ac.kr//jsp/common/DcLoOrgPer.jsp?sItemId=000000009563ko_KR
Appears in Collections:
3. Thesis (학위논문) > 1. School of Medicine (의과대학) > 박사
Full Text
http://dcollection.kmu.ac.kr//jsp/common/DcLoOrgPer.jsp?sItemId=000000009563
File in this Item
There are no files associated with this item.


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE