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Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and hemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischemia
백서의 일과성 전뇌허혈 모델에서 sevoflurane 후처치 후 PKC 경로를 통한 Nrf2와 HO-1의 발현 증가

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Authors
이한나
Advisor
박희평
Major
의과대학 의학과
Issue Date
2015-02
Publisher
서울대학교 대학원
Keywords
Anestheticsinhalation
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 박희평.
Abstract
Introduction: The antioxidant mechanism of sevoflurane postconditioning-induced neuroprotection remains unclear. We determined whether sevoflurane postconditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defense genes) and heme oxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation in a rat model of transient global cerebral ischemia/reperfusion (IR) injury.

Methods: 86 rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane postconditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor
5 mg kg-1 intravenous administration, n=20), and sevoflurane postconditioning plus chelerythrine (n=20). Each group was further divided into two subgroups, based on the day of sacrifice (1 or 7 days after ischemia), of 10 rats each, except sham group (n=3). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed.

Results: On day 1 post-ischemia, but not day 7, Nrf2 and HO-1 expression was significantly higher in the sevoflurane postconditioning group than in the control group. Chelerythrine administration reduced Nrf2 and HO-1 expression induced by sevoflurane postconditioning.

Conclusions: Sevoflurane postconditioning increased Nrf2/HO-1 expression via PKC signaling in the early phase after transient global cerebral IR injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane postconditioning-induced neuroprotection in the early phase after cerebral IR injury.
Language
English
URI
https://hdl.handle.net/10371/122027
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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