左乙拉西坦对缺氧缺血性脑损伤新生大鼠的神经保护作用及氧化应激反应的影响

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (4): 545-550.

左乙拉西坦对缺氧缺血性脑损伤新生大鼠的神经保护作用及氧化应激反应的影响

王海滨¹, 门庆玲², 蔡艳丽¹, 周文龙¹, 郭海志¹, 陈瑞祥^3*

资阳市第一人民医院 1.神经内科; 2.心血管内科,四川资阳 641300;
3.云南省第三人民医院药剂科,云南昆明 650011

收稿日期:2020-05-23 修回日期:2020-07-31 出版日期:2021-04-05 发布日期:2021-04-05
通讯作者: ^*wbo141@163.com
基金资助:
云南中医学院应用基础研究联合专项(2018FF001)

Effects of levetiracetam on neuroprotection and oxidative stress in neonatal rats with hypoxic-ischemic brain damage

WANG Hai-bin¹, MEN Qing-ling², CAI Yan-li¹, ZHOU Wen-long¹, GUO Hai-zhi¹, CHEN Rui-xiang^3*

1. Department of Neurology; 2. Department of Cardiology, the First People's Hospital of Ziyang City, Ziyang 641300;
3. Department of Pharmacy, the Third People's Hospital of Yunnan Province, Kunming 650011, China

Received:2020-05-23 Revised:2020-07-31 Online:2021-04-05 Published:2021-04-05
Contact: ^*wbo141@163.com

摘要/Abstract

摘要： 目的研究左乙拉西坦(LEV)对缺血缺氧性脑损伤(HIBD)新生大鼠的神经保护作用。方法构建HIBD新生大鼠模型,将其随机分成:模型组(model组)、LEV低、中、高浓度组[L、M、H LEV组,分别灌胃10、30、50 mg/(kg·d) LEV],每组各10只,另选10只为假手术组(sham组)。末次给药24 h后,HE染色观察脑组织病变,TUNEL法检测神经元凋亡,ELISA法检测血清中炎性因子白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)及氧化应激因子丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,Western blot检测脑组织半胱氨酸蛋白酶-3(caspase-3)、B淋巴细胞瘤-2(Bcl-2)、核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)蛋白表达。结果与sham组相比,model组大鼠脑组织细胞排列紊乱呈弥漫性分布,空泡化增加,出现炎性浸润,神经元凋亡率、血清IL-6、TNF-α、MDA含量和脑组织caspase-3蛋白表达显著升高(P＜0.05),血清SOD活性、脑组织Bcl-2、Nrf2、HO-1蛋白表达显著降低(P＜0.05);与model组相比,L、M、H LEV组以上变化显著减轻(P＜0.05)。结论 LEV减轻炎性反应、氧化应激,对HIBD新生大鼠发挥神经保护作用。

关键词: 左乙拉西坦, 新生大鼠, 神经元细胞, 氧化应激

Abstract: Objective To study the neuroprotective effect of levetiracetam (LEV) with hypoxia ischemia brain-damage (HIBD) model of neonatal rats. Methods The rats were randomly divided into three groups: model group, LEV low, medium and high concentration groups [gavage with 10, 30, 50 mg/(kg·d) LEV], with 10 rats in each, and another 10 rats in sham operation group. Twenty four hours after the last administration, HE staining was used to observe the pathological changes of rat brain, TUNEL method was used to detect the apoptosis of neurons, the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α(TNF-α), and oxidative stress factors malondialdehyde(MDA), the content and activity of superoxide dismutas (SOD) in serum were detected by ELISA, and the protein expression of caspase-3, B-cell lymphoma-2(Bcl-2), nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase(HO-1) in rat brain tissue were detected by Western blot. Results Compared with the sham operation group, the morphology of brain tissue cell in the model group were disordered, showed diffuse distribution, increased vacuolation and inflammatory infiltration, the apoptosis rate of neurons, the expression of IL-6, TNF-α, MDA in serum and caspase-3 in brain tissue were significantly higher(P＜0.05), and the expression of SOD in serum, Bcl-2, Nrf2 and HO-1 in brain tissue were significantly lower(P＜0.05); Compared with the model group, the above changes of LEV in low, medium and high concentration groups were significantly reduced(P＜0.05). Conclusions LEV can alleviate inflammatory reaction and oxidative stress, and play a neuroprotective role in HIBD newborn rats.

Key words: levetiracetam, neonatal rats, neuronal cells, oxidative stress

中图分类号:

R741

王海滨, 门庆玲, 蔡艳丽, 周文龙, 郭海志, 陈瑞祥. 左乙拉西坦对缺氧缺血性脑损伤新生大鼠的神经保护作用及氧化应激反应的影响[J]. 基础医学与临床, 2021, 41(4): 545-550.

WANG Hai-bin, MEN Qing-ling, CAI Yan-li, ZHOU Wen-long, GUO Hai-zhi, CHEN Rui-xiang. Effects of levetiracetam on neuroprotection and oxidative stress in neonatal rats with hypoxic-ischemic brain damage[J]. Basic & Clinical Medicine, 2021, 41(4): 545-550.

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