2-Iodomelatonin上调NRF2表达对缺血性脑损伤神经保护作用
Up-regulation of NRF2 by 2-Iodomelatonin plays a neuroprotective role in ischemic brain injury
高云奕 1罗倩 1万芪1
作者信息
- 1. 青岛大学神经再生与康复研究院,山东青岛 266071
- 折叠
摘要
目的 探讨褪黑激素受体1(MT1)激动剂2-Iodomelatonin通过上调核因子E2相关因子2(NRF2)对大脑中动脉栓塞小鼠的神经保护作用.方法 采用大脑中动脉栓塞(MCAO)法制备小鼠缺血性脑损伤体内模型,给予2-Iodomelatonin及NRF2抑制剂(Nrf2-IN-1)干预.采用三苯基氯化四氮唑(TTC)染色法检测小鼠大脑的梗死体积,Western Blot法检测缺血损伤后大脑皮质半暗带NRF2表达水平,改良神经功能缺损程度评分(mNSS)评估2-Iodomelatonin和Nrf2-IN-1干预对小鼠缺血性脑损伤亚急性期运动功能的影响.结果 TTC染色结果显示,2-Iodomelatonin干预可以显著降低缺血性脑损伤小鼠的大脑梗死体积(F=7.79,q=5.06,P＜0.05).Western Blot结果显示,2-Iodomelatonin干预可上调小鼠皮质梗死半暗带NRF2的表达水平(F=10.56,q=3.99,P＜0.05).mNSS评分结果显示,2-Iodomelatonin干预可以显著改善缺血性脑损伤第14天的运动功能损伤(F=6.12,q=4.79,P＜0.05),该效应可被 Nrf2-IN-1 逆转(q=3.60,P＜0.05).结论 2-Iodomelatonin 干预可以通过上调NRF2降低缺血性脑损伤小鼠的大脑梗死体积并改善14 d时的运动功能损伤.
Abstract
Objective To study the neuroprotective effect of 2-Iodomelatonin as the agonist of melatonin receptor 1 in mice with middle cerebral artery occlusion by up-regulating nuclear factor erythroid 2-related factor 2(NRF2).Methods The in vivo model of ischemic brain injury in mice was constructed by middle cerebral artery occlusion(MCAO).The interventions consisted of 2-Iodomelatonin and NRF2 inhibitor(Nrf2-IN-1).The infarct volume in mouse brain was determined by triphenyl tetrazolium chlo-ride staining.Western Blot was used to measure the expression levels of NRF2 in the cerebral cortical penumbra after ischemic brain injury.The effects of 2-Iodomelatonin and Nrf2-IN-1 on the motor function of mice in the subacute stage of ischemic brain in-jury were evaluated by the modified neurological deficit score(mNSS).Results The staining showed that 2-Iodomelatonin could significantly reduce the cerebral infarct volume in mice with ischemic brain injury(F=7.79,q=5.06,P＜0.05).Western Blot showed that 2-Iodomelatonin up-regulated the expression level of NRF2 in the cerebral cortical penumbra in mice(F=10.56,q=3.99,P＜0.05).The mNSS scores showed that 2-Iodomelatonin could significantly improve the motor functions at 14 d after ische-mic brain injury(F=6.12,q=4.79,P＜0.05),and this effect could be reversed by Nrf2-IN-1(q=3.60,P＜0.05).Conclusion 2-Iodomelatonin can reduce cerebral infarct volume and improve 14-day motor function in mice with ischemic brain injury by up-re-gulating NRF2.
关键词
缺血性卒中/神经保护/褪黑素/受体,褪黑激素,MT1/2-IodomelatoninKey words
ischemic stroke/neuroprotection/melatonin/receptors,melatonin,MT1/2-Iodomelatonin引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据