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电针对缺血性中风后小胶质细胞极化的调控作用及其长链非编码 RNA 调控 hippo 通路的机制研究。

Electroacupuncture regulates microglia polarization via lncRNA-mediated hippo pathway after ischemic stroke.

机构信息

Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of TCM, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Biotechnol Genet Eng Rev. 2023 Oct;39(2):1379-1395. doi: 10.1080/02648725.2023.2177046. Epub 2023 Feb 9.

Abstract

Microglia polarization and microglia-mediated inflammation play a crucial role in the development of ischaemic brain injury. Electroacupuncture (EA) has the function of anti-inflammatory, which has been thoroughly validated and utilized to treat ischemic brain damage. The fundamental mechanism by which EA alleviates ischemic brain damage by decreasing microglia polarization and microglia-mediated inflammation, however, remains unknown. In the current study, the activation of microglia and inflammatory cytokines was analyzed to confirm the anti-inflammatory function of EA in middle cerebral artery occlusion (MCAO) rats. Whole-transcriptome sequencing was used to examine the differentially expressed lncRNAs in the control, MCAO, and MCAO +EA groups. Our findings demonstrated that EA treatment reduced microglia activation and inflammatory cytokine production. In addition, there are 44 lncRNAs were found significantly different in three groups, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the predicted targets of these lncRNAs suggested that the Hippo pathway may contribute to the development of ischaemic brain injury and to the anti-inflammatory function of EA. Moreover, our data showed that lncRNA TCONS_00022826 (Lnc826) was upregulated in MCAO group, whereas blocked by EA treatment. Furthermore, in vitro OGD cell model data showed that Lnc826 promoted M1 polarization of microglia by regulating the Hippo pathway. Our data suggested that regulating microglia polarization via Lnc826-mediated hippo pathway is a possible mechanism of the EA treatment on ischemic brain injury.

摘要

小胶质细胞极化和小胶质细胞介导的炎症在缺血性脑损伤的发展中起着关键作用。电针(EA)具有抗炎作用,已被彻底验证并用于治疗缺血性脑损伤。然而,EA 通过减少小胶质细胞极化和小胶质细胞介导的炎症来缓解缺血性脑损伤的基本机制尚不清楚。在本研究中,通过分析小胶质细胞的激活和炎症细胞因子来证实 EA 在大脑中动脉闭塞(MCAO)大鼠中的抗炎作用。使用全转录组测序来检查对照、MCAO 和 MCAO+EA 组中差异表达的 lncRNA。我们的研究结果表明,EA 治疗可减少小胶质细胞的激活和炎症细胞因子的产生。此外,在三组中有 44 个 lncRNA 被发现存在显著差异,这些 lncRNA 预测靶基因的京都基因与基因组百科全书(KEGG)通路表明 Hippo 通路可能与缺血性脑损伤的发展以及 EA 的抗炎作用有关。此外,我们的数据显示,lncRNA TCONS_00022826(Lnc826)在 MCAO 组中上调,而被 EA 治疗所阻断。此外,体外 OGD 细胞模型数据表明,Lnc826 通过调节 Hippo 通路促进小胶质细胞 M1 极化。我们的数据表明,通过 Lnc826 介导的 Hippo 通路调节小胶质细胞极化可能是 EA 治疗缺血性脑损伤的一种机制。

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