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Simvastatin protects ischemic spinal cord injury from cell death and cytotoxicity through decreasing oxidative stress : in vitro primary cultured rat spinal cord model under oxygen and glucose deprivation-reoxygenation conditions : 척수 허혈-재관류 손상 시 심바스타틴이 산화스트레스 감소를 통해 세포 사멸 및 세포 독성에 미치는 신경 보호 효과: 산소 및 포도당 결핍-재산소화 생체 외 1차 배양 흰쥐의 척수 모델
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- Authors
- Advisor
- 한성희
- Major
- 의과대학 의학과
- Issue Date
- 2017-08
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (박사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 한성희.
- Abstract
- Background: Ischemia and the following reperfusion damage are critical mechanisms of spinal cord injury. Statins have been reported to decrease ischemia-reperfusion injury in many organs including spinal cord. Anti-oxidative effect is one of the main protective mechanisms of statin against neuronal death and cytotoxicity. We hypothesized that statins anti-oxidative property would yield neuroprotective effects on spinal cord ischemia-reperfusion injury
Methods: Primary cultured spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses. Ischemia–reperfusion injury model was induced by 60 min of oxygen and glucose deprivation (OGD) and 24 h of reoxygenation. Healthy and OGD cells were treated with simvastatin at concentrations of 0.1, 1, and 10 μM for 24 h. Cell viability was assessed using WST-8, cytotoxicity with LDH, and production of free radicals with DCFDA.
Results: OGD reduced neuronal viability compared to normoxic control by 35.3%
however 0.1-10 μM of simvastatin treatment following OGD improved cell survival. OGD increased LDH release up to 214%
however, simvastatin treatment attenuated its cytotoxicity at concentrations of 0.1-10 μM (p < 0.001 and p = 0.001). Simvastatin also reduced deteriorated morphological changes of motor neurons following OGD. Oxidative stress was reduced by simvastatin (0.1-10 μM) compared to untreated cells exposed to OGD (p < 0.001).
Conclusions: Simvastatin effectively reduced spinal cord neuronal death and cytotoxicity against ischemia-reperfusion injury, probably via modification of oxidative stress.
- Language
- English
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