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高频重复经颅磁刺激通过调控 Nrf2/GPx4 信号通路改善血管性痴呆大鼠认知功能。

Enhancement of Cognitive Function in Rats with Vascular Dementia Through Modulation of the Nrf2/GPx4 Signaling Pathway by High-Frequency Repetitive Transcranial Magnetic Stimulation.

机构信息

Department of Rehabilitation Medicine, Nanjing Medical University, Nanjing, China; Rehabilitation Medicine Center, Zhejiang Chinese Medical University Affiliated Jiaxing TCM Hospital, Jiaxing, China.

出版信息

Physiol Res. 2024 Nov 19;73(5):857-868. doi: 10.33549/physiolres.935330.

PMID:39560194
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11629951/
Abstract

Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive therapeutic modality acknowledged for augmenting neurological function recovery following stroke. Nonetheless, uncertainties remain regarding its efficacy in promoting cognitive function recovery in patients diagnosed with vascular dementia (VD). In this study, VD was experimentally induced in a rat model utilizing the bilateral common carotid artery occlusion method. Following a recuperation period of seven days, rats were subjected to high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) at a frequency of 10 Hz. Cognitive function was assessed utilizing the Morris water maze test, and the levels of IL-6, TNF-alpha, SOD, GSH, MDA, and Fe2+ in cerebral tissue were quantitatively analyzed through enzyme-linked immunosorbent assay. Moreover, the gene and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4) were meticulously investigated via quantitative polymerase chain reaction (qPCR) and Western blotting techniques. The use of HF-rTMS notably augmented cognitive function in rats with VD, concomitantly reducing neuroinflammation, oxidative stress, and ferroptosis within the brain. The group subjected to HF-rTMS demonstrated an increase in the levels of both proteins and genes associated with Nrf2 and GPx4, in comparison to the VD group. These results highlight the potential of HF-rTMS treatment in enhancing cognitive function in rats diagnosed with VD through the modulation of the Nrf2/GPx4 signaling pathway. This modulation, in turn, mitigates processes linked with neuroinflammation, oxidative stress, and ferroptosis. Nevertheless, additional studies are essential to comprehensively elucidate the underlying mechanisms and clinical implications of HF-rTMS treatment in the treatment of VD.

摘要

重复经颅磁刺激(rTMS)是一种非侵入性的治疗方法,已被证实可增强中风后神经功能的恢复。然而,其在促进血管性痴呆(VD)患者认知功能恢复方面的疗效仍存在不确定性。在这项研究中,我们使用双侧颈总动脉闭塞法在大鼠模型中诱导 VD。在 7 天的恢复期后,对大鼠进行高频重复经颅磁刺激(HF-rTMS),频率为 10 Hz。使用 Morris 水迷宫测试评估认知功能,并通过酶联免疫吸附试验定量分析脑组织中白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)和 Fe2+的水平。此外,还通过定量聚合酶链反应(qPCR)和 Western blot 技术详细研究了核因子红细胞 2 相关因子 2(Nrf2)和谷胱甘肽过氧化物酶 4(GPx4)的基因和蛋白表达。HF-rTMS 的使用显著提高了 VD 大鼠的认知功能,同时降低了大脑中的神经炎症、氧化应激和铁死亡。与 VD 组相比,接受 HF-rTMS 治疗的大鼠的 Nrf2 和 GPx4 相关蛋白和基因水平均有所增加。这些结果表明,HF-rTMS 治疗通过调节 Nrf2/GPx4 信号通路,有可能增强诊断为 VD 的大鼠的认知功能。这种调节反过来减轻了与神经炎症、氧化应激和铁死亡相关的过程。然而,需要进一步的研究来全面阐明 HF-rTMS 治疗在 VD 治疗中的潜在机制和临床意义。

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