褪黑素对缺氧缺血性脑损伤新生大鼠皮层氧化应激的影响  

Effects of melatonin on cortical oxidative stress in neonatal rats with hypoxic-ischemic brain injury

作　　者：陈亚敏 文政芳[2] 王国霞 Chen Yarnin;Wen Zhengfang;Wang Guoxia(Department of neonatology,Luoyang Maternal and Child Health Hospital,Luoyang 471000;Department of Reproductive Medicine,First Affiliated Hospital of Xinxiang Medical College,Weihui 453100;Institute of Pediatric Diseases,Xi'an Children's Hospital,Xi'an 710043,China)

机构地区：[1]洛阳市妇幼保健院新生儿科,洛阳471000 [2]新乡医学院第一附属医院生殖医学科,卫辉453100 [3]西安市儿童医院儿科疾病研究所,西安710043

出　　处：《神经解剖学杂志》2021年第3期305-309,共5页Chinese Journal of Neuroanatomy

基　　金：西安市儿童医院院级课题(2018E10)。

摘　　要：目的:研究褪黑素(Mel)对缺氧缺血性脑损伤(HIBD)新生大鼠皮层氧化应激的影响及分子机制。方法:54只新生SD大鼠随机分为假手术组(Sham)、缺氧缺血脑损伤组(HIBD)和褪黑素治疗组(HIBD+Mel),利用左侧颈总动脉结扎联合低氧刺激制备新生大鼠HIBD模型,利用神经功能缺损评分(NSS)评测大鼠神经功能变化,通过检测大鼠脑组织含水量评估脑水肿的程度,利用商品化试剂盒检测大鼠大脑皮层反应性活性氧(ROS)的含量,利用Western Blot检测大鼠皮层核因子红细胞2相关因子2(Nrf2)和血红素加氧蛋白-1(HO-1)的表达。结果:与假手术相比,HIBD大鼠神经功能障碍明显(P<0.05),脑含水量增加(P<0.05),ROS增多(P<0.05),皮层中Nrf2和HO-1表达下降(P<0.05)。褪黑素治疗可显著改善HIBD大鼠神经功能(P<0.05),减轻脑水肿和减少ROS含量(P<0.05),促进皮层中Nrf2和HO-1表达。结论:褪黑素通过活化Nrf2/HO-1信号通路减轻HIBD新生大鼠皮层氧化应激水平发挥神经保护作用。Objective:To study the effect and molecular mechanism of melatonin on cortical oxidative stress in neonatal rats with hypoxic ischemic brain injury(HIBD).Methods:Fifty-four 7-day-old newborn SD rats were randomly divided into control group(sham),hypoxic ischemic brain damage(HIBD)and melatonin treatment group(HIBD+Melatonin).Rat HIBD model was established by the left common carotid artery ligation combined hypoxic treatment.The changes of neurological function of rats were evaluated by neurological severity scores(NSS).The degree of brain edema was evaluated by detecting the water content of rat brain tissue.The content of reactive oxygen species(ROS)in the cerebral cortex of rats was detected by commercial kits.The expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in the cerebral cortex of rats was detected by Western Blot.Results:Compared with sham group,HIBD rats showed obvious neurological dysfunction(P<0.05).The brain water content and the level of ROS increased obviously(P<0.05).The expression of Nrf2 and HO-1 down-regulated significantly(P<0.05).Melatonin treatment can significantly improve the neurological function of HIBD rats(P<0.05).The brain water content and the level of ROS were lower than that of HIBD group(P<0.05).Moreover,the expression of Nrf2/HO-1 in cortex was up-regulated significantly compared with HIBD group(P<0.05).Conclusion:Melatonin plays a neuroprotective role by activating Nrf2/HO-1 signaling pathway to reduce the level of cortical oxidative stress in neonatal rats with HIBD.

关 键 词：褪黑素 缺血缺氧性脑病 氧化应激 Nrf2/HO-1信号通路 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]