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M2a 巨噬细胞通过精氨酸酶 1 诱导神经元轴突再生的作用。

The effects of the M2a macrophage-induced axonal regeneration of neurons by arginase 1.

机构信息

Daping Hospital, Army Medical University, State Key Laboratory of Trauma, Burn and Combined Injury, 400042 Chongqing, People's Republic of China.

Xinan Hospital, Army Medical University, 400038 Chongqing, People's Republic of China.

出版信息

Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20193031.

Abstract

BACKGROUND

Spinal cord injury (SCI) is a challenge worldwide, but there are no effective treatments or therapeutic methods in the clinic. Recent studies have shown that type I arginase (Arginase1, Arg1) is closely associated with the treatment of SCI. The classical treatment for SCI involves filling the local area of SCI with activated M2a macrophages to allow the repair and regeneration of some synapses, but the specific mechanism of action of Arg1 is not clear.

METHOD

In the present study, we first induced the polarization of RAW264.7 macrophages to M2a-type cells using IL-4 and constructed an Arg1 knockout cell line through the use of shRNA; we used these cells to treat a rat model of SCI. Finally, the present study explored the mechanism and pathway by which Arginase 1 regulates spinal repair by immunoblotting and immunohistochemistry.

RESULT

Suspended M2a (Arg1-/+) macrophages were transplanted into the injury site in a rat model of contusion SCI. Compared with the model group and the shArg1 group, the shScramble (shSc) group exhibited higher Basso, Beattie, Bresnahan motor function scores, more compact structures and more Nissl bodies. Immunohistochemical results showed that the shSc group expressed higher levels of NeuN (a neuronal marker) and tau (an axonal marker), as well as the up-regulation of Cdc42, N-WASP, Arp2/3 and tau, as determined by Western blot.

CONCLUSION

The study found that the polarization of M2a macrophages promoted the expression of Arginase 1, which restored axonal regeneration, promoted axonal regeneration, and promoted the structural and functional recovery of the contused spinal cord.

摘要

背景

脊髓损伤(SCI)是一个全球性的挑战,但临床上尚无有效的治疗方法或治疗方法。最近的研究表明,I 型精氨酸酶(Arginase1,Arg1)与 SCI 的治疗密切相关。SCI 的经典治疗方法包括用激活的 M2a 巨噬细胞填充 SCI 的局部区域,以允许一些突触的修复和再生,但 Arg1 的具体作用机制尚不清楚。

方法

本研究首先用 IL-4 将 RAW264.7 巨噬细胞诱导极化至 M2a 型细胞,并通过 shRNA 构建 Arg1 敲除细胞系;我们使用这些细胞来治疗 SCI 大鼠模型。最后,本研究通过免疫印迹和免疫组织化学探讨了 Arginase 1 调节脊髓修复的机制和途径。

结果

悬浮的 M2a(Arg1-/-)巨噬细胞被移植到挫伤 SCI 大鼠模型的损伤部位。与模型组和 shArg1 组相比,shScramble(shSc)组的 Basso、Beattie、Bresnahan 运动功能评分更高,结构更紧凑,Nissl 体更多。免疫组织化学结果显示,shSc 组表达更高水平的神经元标志物 NeuN 和轴突标志物 tau,以及 Cdc42、N-WASP、Arp2/3 和 tau 的上调,Western blot 结果也证实了这一点。

结论

本研究发现 M2a 巨噬细胞的极化促进了 Arginase 1 的表达,恢复了轴突再生,促进了轴突再生,并促进了挫伤脊髓的结构和功能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c77/7012653/8fa295abe099/bsr-40-bsr20193031-g1.jpg

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