医学分子生物学杂志 ›› 2023, Vol. 20 ›› Issue (3): 227-231.doi: 10.3870/j.issn.1672-8009.2023.03.007

• 论著 • 上一篇    下一篇

甘草酸通过抑制自噬对脑缺血再灌注后神经元损伤的保护作用

  

  1. 衡水市人民医院神经外科 河北省衡水市, 053000
  • 出版日期:2023-05-31 发布日期:2023-05-29
  • 基金资助:
    衡水市科技计划项目(No. 20220140582) 

Neuroprotective Effect of Glycyrrhizic Acid in Rats with Cerebral Ischemia-reperfusion through Inhibition of Autophagy 

  1. Department of Neurosurgery, Hengshui People’s Hospital, Hengshui, Hebei, 053000, China 
  • Online:2023-05-31 Published:2023-05-29

摘要: 目的 探究甘草酸对脑缺血再灌注神经元损伤的保护作用。 方法 通过在大鼠原代神经元中进 行氧糖剥夺再灌注 (oxygen glucose deprivation reperfusion, OGD/ R) 构建体外脑缺血再灌注模型。 显微镜观 察细胞形态学变化, 免疫荧光染色观察神经元特异性烯醇化酶 (neuron-specific enolase, NSE) 的表达。 使 用甘草酸对损伤神经元进行治疗, CCK-8 法检测神经元细胞的活力变化, 乳酸脱氢酶 (LDH) -细胞毒性检 测试剂盒检测神经元释放的 LDH 水平。 使用 AMPK 激活剂 AICAR 对神经元 AMPK/ mTOR 通路进行激活, Western 印迹检测 AMPK/ mTOR 通路相关蛋白及自噬相关蛋白的表达。 结果 甘草酸抑制 OGD/ R 诱导的神 经元 LDH 水平升高、 细胞活力下降及自噬相关蛋白 Beclin 1、 LC3-Ⅱ的增加, 并抑制 AMPK/ mTOR 通路的 激活。 结论 甘草酸介导 AMPK/ mTOR 通路抑制神经元自噬从而对脑缺血再灌注后神经元发挥保护作用。

关键词: 脑缺血再灌注, 氧糖剥夺再灌注, 甘草酸, 自噬, AMPK/ mTOR, 神经元保护 

Abstract: Objective To investigate the protective effect of glycyrrhizic acid on neurons in rats with cerebral ischemia / reperfusion. Methods An cerebral ischemia-reperfusion model was constructed in rat primary neurons in vitro by oxygen glucose deprivation reperfusion (OGD/ R) method. The changes of cell morphology were observed by microscope, and the expression of neuron-specific enolase ( NSE) was observed by immunofluorescence staining. The damaged neurons were treated with glycyrrhizic acid, and the CCK-8 method was performed to detect the viability of neuronal cells, and the level of LDH released from neurons was detected by using the lactate dehydrogenase (LDH) -cytotoxicity assay kit. The AMPK activator AICAR was used to activate the AMPK/ mTOR pathway in neurons, and the Western blotting assay was used to detect the expression levels of AMPK/ mTOR pathway-related proteins and autophagy-related proteins. Results Glycyrrhizic acid inhibited the OGD/ R-induced enhancement of neuronal LDH level and the expression levels of autophagy-related proteins Beclin 1 and LC3-Ⅱ, and the suppression of cell viability. The OGD/ R induced activation of AMPK/ mTOR pathway was also suppressed after glycyrrhizic acid treatment. Conclusion Glycyrrhizic acid exerts a protective effect on neurons in rats with cerebral ischemia-reperfusion by inhibiting neuronal autophagy through AMPK/ mTOR pathway.

Key words: cerebral ischemia-reperfusion, oxygen glucose deprivation reperfusion, glycyrrhizic acid, autophagy, AMPK/ mTOR, neuron protection

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