基于p62/Keap1/NRF2信号通路探讨针刺对脑出血后脑组织铁死亡调控作用

戴晓红；张宏伟；于薇薇；赵永厚

文章摘要

戴晓红；张宏伟；于薇薇；赵永厚.基于p62/Keap1/NRF2信号通路探讨针刺对脑出血后脑组织铁死亡调控作用[J].中医药信息,2024,41(2):44-50

基于p62/Keap1/NRF2信号通路探讨针刺对脑出血后脑组织铁死亡调控作用

xploration on the Regulatory Effect of Acupuncture on Ferroptosis in Brain Tissue after Cerebral Hemorrhage Based on p62/Keap1/NRF2 Signaling Pathway

投稿时间：2023-09-18 录用日期：2023-11-25

DOI：10.19656/j.cnki.1002-2406.20240208

中文关键词: 脑出血针刺疗法神经功能损伤蛋白表达铁死亡

英文关键词: Cerebral haemorrhage Acupuncture treatment Neurological impairment Protein expression Ferroptosis

基金项目:中国博士后科学基金,国家自然科学基金项目（面上项目，重点项目，重大项目）

作者	单位
戴晓红；张宏伟；于薇薇；赵永厚

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中文摘要:

目的：观察针刺治疗对脑出血大鼠神经功能状态的影响，并基于p62/Keap1/NRF2信号通路研究针刺对脑出血后脑组织铁死亡的调控作用。方法：选用健康正常的雄性SD大鼠33只，随机分为假手术组、模型组和针刺组，每组再分为1 d、3 d和7 d的3个亚组，其中假手术组每个亚组1只大鼠，模型组和针刺组每个亚组5只大鼠。除假手术组外，采用大鼠自体血注射的方式建立脑出血大鼠模型；假手术组、针刺组中大鼠脑组织可选择采用由百会穴刺向曲鬓穴的刺灸方法，采用Ludmila Belayev神经功能评分来评估模型各组中大鼠神经功能系统的功能缺损程度情况；采用Western blot检测脑组织中System Xc - 、GPX4蛋白的表达；用透射电镜观测到了各组大鼠脑组织的神经细胞线粒体形态；酶联免疫吸附方法检测脑组织中MDA、GSH、GPX4含量的变化。结果：由百会穴开始向曲鬓穴进行的针刺方法可以降低脑出血大鼠体内的Ludmila Belayev神经功能的评分，从而缓解了脑出血大鼠神经肌肉传导缺损症；不同时间点相比较，大鼠System Xc - 相对表达量在3 d和7 d均高于1 d，假手术组和针刺组整体表现为随着时间增加System Xc - 蛋白量不断增加。与假手术组比较，模型组大鼠的MDA水平明显升高（P < 0.05）；GSH、GPX4水平均明显降低（P < 0.05）；在同一时间点与模型组相比较，针刺组大鼠MDA水平均明显降低（P < 0.05）；GSH、GPX4水平均明显升高（P < 0.05）。模型组和针刺组大鼠在3 d MDA水平达到高峰，7 d MDA水平下降。GSH、GPX4水平则不断升高。结论：针刺可改善急性脑出血大鼠神经肌肉损伤神经功能，通过降低MDA、升高System Xc - 、GSH、GPX4蛋白表达水平抑制脑出血大鼠神经细胞铁死亡，在脑出血治疗中发挥脑保护作用。

英文摘要:

Objective：To observe the effect of acupuncture treatment on the neurological function of rats with cerebral hemorrhage， and to explore the regulatory effect of acupuncture on ferroptosis in brain tissue after cerebral hemorrhage based on the p62/Keap1/NRF2 signaling pathway. Method： A total of 33 healthy and normal male SD rats were selected and randomly divided into sham surgery group， model group， and acupuncture group. Each group was further divided into three subgroups： subgroups on day 1， day 3， and day 7， with one rat in each subgroup of the sham surgery group， and five rats in each subgroup of the model group and acupuncture group. Except for the sham surgery group， all other groups used autologous blood injection to establish a rat model of cerebral hemorrhage. The brain tissue of rats in sham operation group and acupuncture group was stimulated by inserting a needle from Baihui point to Qubin point and Ludmila Belayev neural function score was used to evaluate the degree of functional impairment of rat neural function system in each model group.The expressions of System Xc - and GPX4 proteins in brain tissue were detected by Western blot. The mitochondrial morphology of nerve cells in the brain tissues of rats in each group was observed using transmission electron microscopy. Enzyme linked immunosorbent assay （ELISA） was used to detect changes in MDA， GSH，and GPX4 levels in brain tissue. Result： The acupuncture method of inserting a needle from Baihui point to Qubin point could reduce the Ludmila Bellayev neural function score in rats with cerebral hemorrhage， thereby alleviating neuromuscular conduction defects in rats with cerebral hemorrhage. The relative expression level of System Xc - protein in rats was higher on day 3 and day 7 than on day 1， and the amount of System Xc - protein increased with time in the groups of sham surgery and acupuncture groups. Compared with the sham surgery group， the MDA levels of the model group rats significantly increased （P < 0.05）， and the levels of GSH and GPX4 significantly decreased （P < 0.05）. Compared with model group at the same time point， MDA levels in acupuncture group significantly decreased （P < 0.05）， while， GSH and GPX4 levels significantly increased （P < 0.05）. The MDA levels of the model group and acupuncture group reached their peak on day 3， started to decrease on day 7， while， the levels of GSH and GPX4 continue to rise. Conclusion： Acupuncture can improve neuromuscular injury and neurological function in rats with acute cerebral hemorrhage. It can inhibit neuronal cell ferroptosis by reducing MDA， increasing the expression levels of System Xc - ， GSH， and GPX4 proteins，and play a neuroprotective role in the treatment of cerebral hemorrhage.

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