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针刺减轻大鼠脑出血后神经元细胞死亡、炎症和铁死亡,并下调 miR-23a-3p。

Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats.

机构信息

First Ward of Acupuncture and Moxibustion Department, Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150001, China.

Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150001, China.

出版信息

J Mol Neurosci. 2021 Sep;71(9):1863-1875. doi: 10.1007/s12031-020-01770-x. Epub 2021 Jan 5.

DOI:10.1007/s12031-020-01770-x
PMID:33403590
Abstract

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.

摘要

百会透曲鬓针刺法常用于中国治疗脑出血(ICH)。针刺会影响多种疾病相关的 microRNAs。已有研究表明,microRNA-23a-3p(miR-23a-3p)在 ICH 患者中上调。本研究探讨了百会透曲鬓针刺法对 ICH 后 miR-23a-3p 表达的影响,以及 miR-23a-3p 在 ICH 中的作用。通过将自体血注入尾状核诱导大鼠 ICH 模型。ICH 后每天进行一次针刺,每次 30 分钟,连续 3 天。针刺 3 天后,分析大鼠的神经行为功能、脑水肿、神经元细胞死亡、炎症、铁死亡、核因子 E2 样 2(NFE2L2)信号通路和脑组织中 miR-23a-3p 水平。此外,在 ICH 建模前 3 天向大鼠注射 antagomiR-23a-3p,以分析 miR-23a-3p 在神经元细胞死亡、炎症、铁死亡和 NFE2L2 信号通路中的作用。针刺减轻了 ICH 引起的神经功能缺损、脑含水量增加和 Fluoro-Jade B(FJB)阳性细胞增加以及促炎细胞因子的释放。针刺还减轻了铁死亡,降低了 miR-23a-3p 的表达,表现为 NFE2L2 核易位增加、血红素加氧酶-1 和谷胱甘肽过氧化物酶 4 的表达增加,铁和丙二醛含量以及活性氧积累减少。此外,antagomiR-23a-3p 抑制了 ICH 引起的 FJB 阳性细胞增加、促炎细胞因子释放、铁死亡和 NFE2L2 激活。值得注意的是,miR-23a-3p 的结合位点存在于 NFE2L2 中。综上所述,针刺可能通过下调 miR-23a-3p 减轻 ICH 后神经元细胞死亡、炎症和铁死亡。本研究为百会透曲鬓针刺改善 ICH 后早期损伤提供了潜在机制。

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