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发动蛋白2基因修饰的嗅鞘细胞对大鼠脊髓损伤后功能及分子神经保护的作用

Effect of Dynamin-2 Gene Modified OECs on Functional and Molecular Neuroprotection After Spinal Cord Injury in Rats.

作者信息

Yin Zhijie, Zhang Zhiyong, Li Haiming, Zhang Xingping, Jin Baozhe

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.

The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830099, China.

出版信息

Neurochem Res. 2025 Jul 16;50(4):232. doi: 10.1007/s11064-025-04491-y.

Abstract

Spinal cord injury (SCI) imposes a significant economic burden on individuals and society, with limited options for repairing the central nervous system after injury. Cell transplantation therapy, particularly using olfactory ensheathing cells (OECs), has shown promise. However, the neuroprotective mechanisms underlying genetically modified OECs remain unclear. This study aimed to investigate the effects of Dynamin-2 (Dnm2) gene-modified OECs (Dnm2-OECs) on SCI repair in a rat model. OECs were harvested from three-day-old rats. Adult rats were divided into sham, SCI, SCI-OEC, and SCI-Dnm2-OECs groups. Dnm2-OECs were transplanted one day post-SCI model, and recovery was assessed through BBB scores, histological analyses, and molecular markers of inflammation. Results showed that the purity and infection efficiency of OECs were 87.28 ± 7.65% and 89.04 ± 5.56%, respectively. Dnm2-OECs survived for at least 28 days post-transplantation and significantly improved BBB scores by day 21. Additionally, neuronal counts increased, syringomyelia decreased, demyelination lessened, and mitochondrial structure improved. Dnm2 levels rose in spinal tissue, while NF-κB pathway proteins and pro-inflammatory cytokines (TRAF6, IL-17, IL-1β and TNF-α) were reduced. Microglial cells (Iba1) decreased correspondingly. These results indicate that Dnm2-OECs transplantation enhances neurological recovery after by inhibiting the NF-κB signaling pathway, offering a potential therapeutic strategy for SCI repair.

摘要

脊髓损伤(SCI)给个人和社会带来了沉重的经济负担,损伤后修复中枢神经系统的选择有限。细胞移植疗法,特别是使用嗅鞘细胞(OECs),已显示出前景。然而,基因修饰的OECs的神经保护机制仍不清楚。本研究旨在探讨动力蛋白2(Dnm2)基因修饰的OECs(Dnm2-OECs)对大鼠脊髓损伤修复的影响。从3日龄大鼠中获取OECs。成年大鼠分为假手术组、脊髓损伤组、脊髓损伤-OECs组和脊髓损伤-Dnm2-OECs组。在脊髓损伤模型后1天移植Dnm2-OECs,并通过BBB评分、组织学分析和炎症分子标志物评估恢复情况。结果显示,OECs的纯度和感染效率分别为87.28±7.65%和89.04±5.56%。Dnm2-OECs在移植后至少存活28天,并在第21天时显著提高了BBB评分。此外,神经元数量增加,空洞症减少,脱髓鞘减轻,线粒体结构改善。脊髓组织中Dnm2水平升高,而NF-κB通路蛋白和促炎细胞因子(TRAF6、IL-17、IL-1β和TNF-α)减少。小胶质细胞(Iba1)相应减少。这些结果表明,Dnm2-OECs移植通过抑制NF-κB信号通路增强了神经恢复,为脊髓损伤修复提供了一种潜在的治疗策略。

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