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牛磺熊去氧胆酸诱导的 M2 表型巨噬细胞移植促进大鼠脊髓损伤后的抗炎作用和功能恢复。

Transplantation of tauroursodeoxycholic acid-inducing M2-phenotype macrophages promotes an anti-neuroinflammatory effect and functional recovery after spinal cord injury in rats.

机构信息

Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea.

Department of Biomedical Science, CHA University, Seongnam-si, Korea.

出版信息

Cell Prolif. 2021 Jun;54(6):e13050. doi: 10.1111/cpr.13050. Epub 2021 May 7.

Abstract

OBJECTIVES

In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)-induced M2-phenotype (M2) macrophages and their ability to promote anti-neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model.

METHODS

To this end, compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF), we evaluated whether TUDCA effectively differentiates bone marrow-derived macrophages (BMDMs) into M2 macrophages.

RESULTS

The M2 expression markers in the TUDCA-treated BMDM group were increased more than those in the GM-CSF-treated BMDM group. After the SCI and transplantation steps, pro-inflammatory cytokine levels and the mitogen-activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA-induced M2 group more than they were in the GM-CSF-induced M1 group and in the TUDCA group. Moreover, the TUDCA-induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM-CSF-induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)-labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA-induced M2 group more than those in the GM-CSF-induced M1 group and the TUDCA group.

CONCLUSIONS

This study demonstrates that the transplantation of TUDCA-induced M2 macrophages promotes an anti-neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA-induced M2 macrophages represents a possible alternative cell therapy for SCI.

摘要

目的

在本研究中,我们研究了熊去氧胆酸(TUDCA)诱导的 M2 表型(M2)巨噬细胞的移植及其在脊髓损伤(SCI)模型中促进抗神经炎症作用和功能恢复的能力。

方法

为此,我们评估了 TUDCA 是否比粒细胞-巨噬细胞集落刺激因子(GM-CSF)更有效地将骨髓来源的巨噬细胞(BMDM)分化为 M2 巨噬细胞。

结果

TUDCA 处理的 BMDM 组中的 M2 表达标志物的增加量高于 GM-CSF 处理的 BMDM 组。在 SCI 和移植步骤之后,TUDCA 诱导的 M2 组中的促炎细胞因子水平和丝裂原激活蛋白激酶(MAPK)途径明显低于 GM-CSF 诱导的 M1 组和 TUDCA 组。此外,与 GM-CSF 诱导的 M1 组和 TUDCA 组相比,TUDCA 诱导的 M2 组显示出明显增加的组织体积和改善的运动功能。此外,TUDCA 诱导的 M2 组中的生物素化葡聚糖胺(BDA)标记的皮质脊髓束(CST)轴突和神经元核标志物(NeuN)水平高于 GM-CSF 诱导的 M1 组和 TUDCA 组。

结论

本研究表明,TUDCA 诱导的 M2 巨噬细胞的移植促进了 SCI 中的抗神经炎症作用和运动功能恢复。因此,我们建议 TUDCA 诱导的 M2 巨噬细胞的移植代表了 SCI 细胞治疗的一种可能替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6971/8168422/a60bcf153507/CPR-54-e13050-g002.jpg

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