Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats
Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats
复制标题
针灸可改善大鼠脑出血后神经元细胞死亡、炎症和铁死亡以及 miR-23a-3p 下调
DOI：
10.1007/s12031-020-01770-x
复制
发表时间：
2021-01-05
影响因子：
3.1
通讯作者：
Zou, Wei
中科院分区：
文献类型：
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作者：
Kong, Ying;Li, Shulin;Zou, Wei
百会穴透刺曲滨穴是我国治疗脑出血的常用针刺法。针灸影响疾病中的多种microRNA。MicroRNA-23 a-3 p（miR-23 a-3 p）已被证明在ICH患者中上调。本文就针刺百会穴透屈滨穴对脑出血后miR-23 a-3 p表达的影响及miR-23 a-3 p在脑出血中的作用进行探讨。采用尾状核内注入自体血的方法建立大鼠脑出血模型。连续针刺3 d后，观察各组大鼠神经行为功能、脑水肿、神经元细胞死亡、炎症反应、铁凋亡、核因子E2样2（NFE 2L 2）信号通路及脑组织中miR-23 a-3 p水平的变化。此外，在ICH建模前3天将miR-23 a-3 p注射到大鼠中，以分析miR-23 a-3 p在神经元细胞死亡、炎症、铁凋亡和NFE 2L 2信号传导中的功能。针刺可减轻ICH引起的神经功能缺损，增加脑含水量和Fluoro-Jade B（FJB）阳性细胞，释放促炎细胞因子。针刺还减轻了铁凋亡，降低了miR-23 a-3 p的表达，表现为增加NFE 2L 2核转位和血红素氧合酶-1和谷胱甘肽过氧化物酶4的表达，降低了铁和丙二醛含量以及活性氧的积累。此外，EkomiR-23 a-3 p抑制ICH诱导的FJB阳性细胞的增加、促炎细胞因子的释放、铁凋亡，并促进NFE 2L 2活化。值得注意的是，miR-23 a-3 p的结合位点存在于NFE 2L 2中。综上所述，针刺可能通过下调miR-23 a-3 p减轻脑出血后神经细胞死亡、炎症和铁凋亡。本研究为百会穴透刺祛病针法改善脑出血后早期损伤提供了可能的机制。
Baihui-penetrating-Qubin acupuncture is frequently used to treat intracerebral hemorrhage (ICH) in China. Acupuncture affects multiple microRNAs in diseases. MicroRNA-23a-3p (miR-23a-3p) has been demonstrated to be up-regulated in ICH patients. Herein, the effect of Baihui-penetrating-Qubin acupuncture on miR-23a-3p expression after ICH and the role of miR-23a-3p in ICH were discussed. A rat model of ICH was induced by infusing autologous blood into caudate nucleus. Acupuncture was performed after ICH once a day for 30 min. After 3 consecutive days of acupuncture, the neurobehavioral function, brain edema, neuronal cell death, inflammation, ferroptosis, nuclear factor E2-like 2 (NFE2L2) signaling and miR-23a-3p levels in brain tissues were analyzed. Additionally, antagomiR-23a-3p was injected into rats 3 days prior to ICH modeling to analyze the function of miR-23a-3p in neuronal cell death, inflammation, ferroptosis, and NFE2L2 signaling. Acupuncture relieved the ICH-induced neurological function deficits, increases in brain water content and Fluoro-Jade B (FJB)-positive cells and release of proinflammatory cytokines. Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. This study provides a potential mechanism underlying the Baihui-penetrating-Qubin acupuncture improving the early injury after ICH.