硫化氢对氧糖剥夺/复氧神经元细胞自噬和凋亡的作用研究

doi:10.13418/j.issn.1001-165x.2021.04.012

中国临床解剖学杂志 ›› 2021, Vol. 39 ›› Issue (4): 426-430.doi: 10.13418/j.issn.1001-165x.2021.04.012

硫化氢对氧糖剥夺/复氧神经元细胞自噬和凋亡的作用研究

蒋文武^{1, 2}，洪岳³，　邬力祥²，　邓吕红⁴

1.南方医科大学第五附属医院神经外科，广州 510920； 2.中南大学基础医学院生理学系，长沙 410013；
3.南华大学附属第一医院神经外科，湖南衡阳 421001； 4.南方医科大学第五附属医院眼科，广州 510920

收稿日期:2020-04-05 出版日期:2021-07-25 发布日期:2021-07-25
作者简介:蒋文武（1972-），男，湖南衡阳人，博士，副主任医师，主要从事神经外科临床治疗和基础研究，E-mail：jiangwenwu0820@163.com
基金资助:
国家自然科学基金（81472160）

Effects of hydrogen sulfide on the autophagy and apoptosis induced by oxygen-glucose deprivation-reoxygenation in rat neuron

Jiang Wenwu^1,2, Hong Yue³, Wu Lixiang², Deng Lvhong⁴

1. Department of Neurological Surgery, the Fifth Affiliated Hospital of Southern Medical University, Guangzhou, 510920, China; 2. Department of Physiology, School of Basic Medicine, Central South University, Changsha 410013, China; 3. Department of Neurological Surgery, the First Affiliated Hospital of University of South China, Hengyang 421001, China; 4. Department of Ophthalmology, the Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510920, China

Received:2020-04-05 Online:2021-07-25 Published:2021-07-25

摘要/Abstract

摘要： 目的　探讨外源性硫化氢（H2S）对氧糖剥夺／复氧（OGD/R）诱导的神经元细胞自噬和损伤的影响，明确H2S减轻大鼠脑缺血再灌注损伤的分子机制。方法　以大鼠神经元PC12细胞为研究对象，采用经典的OGD/R诱导细胞损伤，硫氢化钠（NaHS）作为H2S的供体预处理后观察H2S对OGD/R诱导的细胞自噬抑制蛋白mTOR、AMPK及其磷酸化AMPK的影响。为明确AMPK在H2S调节PC12细胞自噬中的作用，采用AMPK过表达质粒进行干预，并观察其对H2S减轻PC12细胞损伤的影响。结果　OGD/R处理的PC12细胞mTOR磷酸化水平降低、AMPK活性增强，NaHS预处理可部分逆转上述改变。而AMPK过表达后，可消除NaHS对OGD/R诱导的自噬和细胞凋亡的抑制作用。结论　H2S可通过抑制AMPK活化，进而抑制缺血再灌注时大脑神经元过度的自噬和凋亡，最终减轻神经元损伤。

关键词: 硫化氢, 　自噬, 　氧糖剥夺/复氧, 　硫氢化钠

Abstract: Objective　To investigate the effects of exogenous hydrogen sulfide (H2S) on autophagy and injury induced by oxygen glucose deprivation/reoxygenation (OGD/R) in neurons, and to clarify the molecular mechanism of H2S attenuating cerebral ischemia-reperfusion injury in rats.　Methods　Rat neuronal PC12 cells were used as the research object. Classical OGD/R was used to induce cell damage. Sodium thiosulfate (NaHS), a donor of H2S, was used to observe the effect of H2S on OGD/R-induced mTOR, AMPK and its phosphorylated AMPK. In order to clarify the role of AMPK in the regulation of autophagy in PC12 cells by H2S, AMPK overexpression plasmid was used to observe the effect of H2S on the damage of PC12 cells.　Results　The OGD/R-treated PC12 cells had decreased mTOR phosphorylation level and enhanced AMPK activity, and NaHS pretreatment partially reversed the above changes. The overexpression of AMPK can abolish the inhibitory effect of NaHS on OGD/R-induced autophagy and cell damage. Conclusions　H2S can inhibit the autophagy of brain neurons during ischemia-reperfusion by inhibiting the activation of AMPK, and finally reduce neuronal damage.

Key words: , Hydrogen sulfide, Autophagy, 　Oxygen-glucose deprivation-reoxygenation, 　Sodium hydrosulfide

中图分类号:

R743.33

蒋文武, 洪岳, 邬力祥, 邓吕红. 硫化氢对氧糖剥夺/复氧神经元细胞自噬和凋亡的作用研究[J]. 中国临床解剖学杂志, 2021, 39(4): 426-430.

Jiang Wenwu, Hong Yue, Wu Lixiang, Deng Lvhong. Effects of hydrogen sulfide on the autophagy and apoptosis induced by oxygen-glucose deprivation-reoxygenation in rat neuron[J]. Chinese Journal of Clinical Anatomy, 2021, 39(4): 426-430.

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硫化氢对氧糖剥夺/复氧神经元细胞自噬和凋亡的作用研究

Effects of hydrogen sulfide on the autophagy and apoptosis induced by oxygen-glucose deprivation-reoxygenation in rat neuron

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