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骨髓间充质干细胞条件培养基通过抑制 Gal-3/NLRP3 和 M1 小胶质细胞/巨噬细胞极化缓解脊髓损伤。

Conditioned medium from bone marrow mesenchymal stem cells relieves spinal cord injury through suppression of Gal-3/NLRP3 and M1 microglia/macrophage polarization.

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.

Department of Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, PR China.

出版信息

Pathol Res Pract. 2023 Mar;243:154331. doi: 10.1016/j.prp.2023.154331. Epub 2023 Jan 23.

Abstract

The therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) and their conditioned media have been well-documented. This study focused on the effects of BMSC-conditioned medium (BMSCcm) on spinal cord injury (SCI). To study the effects of BMSCcm on rat motor function, inflammatory response, and M1/M2 macrophage/microglial polarization, SCI model rats were treated with BMSCcm and vectors for overexpression of galectin-3 (Gal-3) or NLR family pyrin domain containing 3 (NLRP3). Treatment with BMSCcm reduced the expression of Gal-3 and NLRP3, alleviated the inflammatory response, suppressed M1 microglia/macrophage polarization, and triggered M2 microglia/macrophage polarization in SCI model rats. Meanwhile, overexpression of Gal-3 or NLRP3 counteracted the suppressive effect of BMSCcm on SCI. Moreover, during BMSCcm treatment, overexpression of Gal-3 promoted the expression of NLRP3, whereas overexpression of NLRP3 had no significant effect on the expression of Gal-3. Additionally, the effects of BMSCcm on macrophage/microglial polarization and the underlying molecular mechanisms were observed in vitro. This study demonstrated that BMSCcm alleviates SCI by suppressing the expression of Gal-3 and NLRP3.

摘要

骨髓间充质干细胞(BMSCs)及其条件培养基的治疗效果已有充分的文献记载。本研究重点关注 BMSC 条件培养基(BMSCcm)对脊髓损伤(SCI)的影响。为了研究 BMSCcm 对大鼠运动功能、炎症反应以及 M1/M2 巨噬细胞/小胶质细胞极化的影响,将 SCI 模型大鼠用 BMSCcm 和过表达半乳糖凝集素-3(Gal-3)或 NOD、LRR 和富含亮氨酸重复序列蛋白 3(NLRP3)的载体进行处理。BMSCcm 处理可降低 Gal-3 和 NLRP3 的表达,减轻炎症反应,抑制 M1 型小胶质细胞/巨噬细胞极化,并触发 SCI 模型大鼠的 M2 型小胶质细胞/巨噬细胞极化。同时,Gal-3 或 NLRP3 的过表达抵消了 BMSCcm 对 SCI 的抑制作用。此外,在 BMSCcm 处理过程中,Gal-3 的过表达促进了 NLRP3 的表达,而过表达 NLRP3 对 Gal-3 的表达没有显著影响。此外,还在体外观察了 BMSCcm 对巨噬细胞/小胶质细胞极化的影响及其潜在的分子机制。本研究表明,BMSCcm 通过抑制 Gal-3 和 NLRP3 的表达来减轻 SCI。

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