The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down–regulation of the reactive oxygen species―dependent nuclear factor κB pathway
백서의 출혈성 쇼크 모델에서 나이아신의 급성 폐 손상 치료 효과 및 기전 규명: 활성산소종 의존성 nuclear factor κB 경로 억제
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과 응급의학전공, 2016. 2. 서길준.
- Introduction: The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats.
Methods: HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mmHg to 25 mmHg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 (MP1) activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6 and IL-8 levels in the serum.
Results: The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione‒glutathione disulfide ratios
decreased lung malondialdehyde levels
down-regulated the NF-κB pathway
suppressed TNF-α, IL-6 and IL-8 levels in the lung tissue and serum
and attenuated histologic lung damage.
Conclusions: A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species‒dependent NF-κB pathway.