NF-κB信号通路在人脐带间充质干细胞移植对新生大鼠脑白质损伤修复中的作用

doi:10.7499/j.issn.1008-8830.2408099

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Abstract Objective To observe the reparative effects of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation on white matter injury (WMI) in neonatal rats and explore its mechanism through the nuclear factor-kappa B (NF-κB) signaling pathway mediated by microglial cells. Methods Sprague-Dawley rats, aged 2 days, were randomly divided into three groups: sham-operation,WMI, and hUC-MSC (n=18 each). Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in the white matter, and immunofluorescence staining was used to measure the expression level of ionized calcium-binding adapter molecule 1 (Iba1). Western blotting was used to measure the protein expression levels of inhibitory subunit of nuclear factor-kappa B alpha (IκBα), phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), myelin basic protein (MBP), and neuron-specific nuclear protein (NeuN). Quantitative real-time PCR was used to assess the mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), MBP, and NeuN. Immunohistochemistry was used to measure the protein expression levels of MBP and NeuN. On day 28, the Morris water maze test was used to evaluate spatial cognitive ability. Results Fourteen days after modeling, the sham-operation group exhibited intact white matter structure with normal cell morphology and orderly nerve fiber arrangement. In the WMI group, large-scale cell degeneration and necrosis were observed, and nerve fiber arrangement was disordered. The hUC-MSC group showed relatively normal cell morphology and more orderly nerve fibers. Compared with the sham-operation group, the WMI group had significantly higher proportions of Iba1-positive cells, increased protein levels of p-IκBα and p-NF-κB p65, and higher mRNA levels of TNF-α and IL-1β. The protein expression of IκBα and the positive expression of MBP and NeuN, as well as their protein and mRNA levels, were significantly reduced in the WMI group (P<0.05). Compared with the WMI group, the hUC-MSC group showed reduced proportions of Iba1-positive cells, decreased protein levels of p-IκBα and p-NF-κB p65, and lower mRNA levels of TNF-α and IL-1β. Furthermore, IκBα protein expression and MBP and NeuN expression (both at the protein and mRNA levels) were significantly increased in the hUC-MSC group (P<0.05). On day 28, the Morris water maze results showed that compared with the sham-operation group, the WMI group had significantly longer escape latency and fewer platform crossings (P<0.05). In contrast, the hUC-MSC group had significantly shorter escape latency and more platform crossings than the WMI group (P<0.05). Conclusions hUC-MSC transplantation can repair WMI in neonatal rats, promote the maturation of oligodendrocytes, and support neuronal survival, likely by inhibiting activation of the NF-κB signaling pathway mediated by microglial cells.

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	ZHANG Shu-Juan
	WANG Chao
	XU Qian-Qian
	ZHANG Jun
	ZHU Yan-Ping

Key words： Human umbilical cord mesenchymal stem cell White matter injury Nuclear factor-kappa B pathway Neonatal rat

Received: 20 August 2024

Corresponding Authors: Zhu Y-P , Email: 1119788145@qq.com; E-mail: 1119788145@qq.com

Cite this article:

ZHANG Shu-Juan,WANG Chao,XU Qian-Qian et al. Role of the nuclear factor-kappa B signaling pathway in the repair of white matter injury in neonatal rats through human umbilical cord mesenchymal stem cell transplantation[J]. CJCP, 2024, 26(12): 1352-1361.

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http://www.zgddek.com/EN/10.7499/j.issn.1008-8830.2408099 OR http://www.zgddek.com/EN/Y2024/V26/I12/1352

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