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电针对脑缺血再灌注后炎症损伤的作用机制:通过增强 M2 型小胶质细胞 ABCA1 介导的噬作用。

Electroacupuncture reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia.

机构信息

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 1166 Liutai Avenue, Chengdu, 611137, Sichuan, China.

Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, Chengdu, 611137, Sichuan, China.

出版信息

Mol Brain. 2024 Sep 2;17(1):61. doi: 10.1186/s13041-024-01135-0.

DOI:10.1186/s13041-024-01135-0
PMID:39223647
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11367741/
Abstract

Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.

摘要

缺血性脑卒中(IS)是一种严重的脑血管疾病,具有高残疾率和死亡率,其中炎症反应对其进展和预后至关重要。噬作用,即迅速清除死亡细胞,可以减少 IS 损伤后过度的炎症反应。虽然电针(EA)已被证明可以减少缺血/再灌注(I/R)后的炎症反应,但它与噬作用的关系尚不清楚。我们通过分析公共数据集并在小鼠模型中验证发现,鉴定出 ATP 结合盒转运蛋白 A1(Abca1)是 IS 后噬作用吞噬过程的关键调节因子,揭示了它与 IS 进展的密切关系。我们证明,EA 可以减少 I/R 引起的神经元细胞死亡和过度炎症。此外,EA 治疗增加了 Abca1 的表达,防止了小胶质细胞的激活,促进了 M2 小胶质细胞的极化,并增强了它们吞噬 I/R 小鼠损伤神经元的能力。这表明,EA 对噬作用的调节可能是减少脑 I/R 损伤的一种潜在机制,使噬作用步骤的调节剂成为 EA 益处的有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/75a0200473b8/13041_2024_1135_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/9e13f3107a5f/13041_2024_1135_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/e600876d1e71/13041_2024_1135_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/75a0200473b8/13041_2024_1135_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/ad405f487d2c/13041_2024_1135_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/a1ad62ffedc3/13041_2024_1135_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/bf3c62145206/13041_2024_1135_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/9e13f3107a5f/13041_2024_1135_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/e600876d1e71/13041_2024_1135_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f0b/11367741/75a0200473b8/13041_2024_1135_Fig6_HTML.jpg

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本文引用的文献

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Front Immunol. 2024 May 2;15:1319863. doi: 10.3389/fimmu.2024.1319863. eCollection 2024.
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Integrating Bulk RNA and Single-Cell Sequencing Data Unveils Efferocytosis Patterns and ceRNA Network in Ischemic Stroke.整合批量RNA和单细胞测序数据揭示缺血性卒中中的噬菌作用模式和ceRNA网络。
Transl Stroke Res. 2025 Jun;16(3):733-746. doi: 10.1007/s12975-024-01255-8. Epub 2024 Apr 28.
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Electroacupuncture Alleviates Neuroinflammation by Regulating Microglia Polarization via STAT6/PPARγ in Ischemic Stroke Rats.
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Neuroscience. 2023 Nov 10;532:23-36. doi: 10.1016/j.neuroscience.2023.09.007. Epub 2023 Sep 21.
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Electro-acupuncture treatment inhibits the inflammatory response by regulating γδ T and Treg cells in ischemic stroke.电针治疗通过调节缺血性脑卒中中的γδT细胞和调节性T细胞来抑制炎症反应。
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