[1]白杨,杨越,陈方方.Toll样受体4抗体通过抑制炎症与氧化应激改善帕金森病模型小鼠的神经损伤及运动功能障碍[J].陕西医学杂志,2026,(7):888-893,939.[doi:DOI:10.3969/j.issn.1000-7377.2026.07.004]
　BAI Yang,YANG Yue,CHEN Fangfang.TLR4 antibody alleviates dopaminergic neurodegeneration and motor dysfunction in a mouse model of Parkinson’s Disease by suppressing neuroinflammation and oxidative stress[J].,2026,(7):888-893,939.[doi:DOI:10.3969/j.issn.1000-7377.2026.07.004]
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Toll样受体4抗体通过抑制炎症与氧化应激改善帕金森病模型小鼠的神经损伤及运动功能障碍

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年7期
页码:
888-893,939
栏目:
基础研究
出版日期:
2026-07-05

文章信息/Info

Title:
TLR4 antibody alleviates dopaminergic neurodegeneration and motor dysfunction in a mouse model of Parkinson’s Disease by suppressing neuroinflammation and oxidative stress
作者:
白杨; 杨越; 陈方方
（新疆医科大学第五附属医院神经内科，新疆 乌鲁木齐 830054）
Author(s):
BAI Yang; YANG Yue; CHEN Fangfang
（Department of Neurology,Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830054，China）
关键词:
帕金森病; Toll样受体4抗体; 神经炎症; 氧化应激; 多巴胺能神经元; 核因子κB; 核因子E2相关因子2/血红素氧合酶1通路
Keywords:
Parkinson’s disease; TLR4 antibody; Neuroinflammation; Oxidative stress; Dopaminergic neurons; Nuclear factor-κB; Nuclear factor erythroid 2-related factor 2/Heme oxygenase 1 pathway
分类号:
R 742
DOI:
DOI:10.3969/j.issn.1000-7377.2026.07.004
文献标志码:
A
摘要:
目的：探讨Toll样受体 4（TLR4）抗体对帕金森病(PD) 模型小鼠运动功能、神经病理损伤的影响，并阐明其潜在分子机制。方法：采用6-羟基多巴胺建立PD小鼠模型，随机分为对照组、PD模型组和PD模型+TLR4抗体组。通过步态分析和旷场实验评估小鼠运动功能；免疫组化检测黑质区酪氨酸羟化酶（TH）表达；TUNEL法检测细胞凋亡水平；ELISA 法检测氧化应激指标及炎症因子水平；RT-qPCR和Western blot分析Toll样受体4（TLR4）/肿瘤坏死因子受体相关因子6（TRAF6）/核因子E2相关因子 2（Nrf2）/血红素氧合酶1（HO-1）信号通路及凋亡相关分子的表达变化。结果：与PD模型组比较，TLR4抗体干预显著改善PD小鼠的运动功能障碍，提高黑质区TH表达并减少细胞凋亡。分子机制研究显示，TLR4抗体可显著抑制TLR4/TRAF6及下游核因子-κB（NF-κB）信号激活，降低白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）等促炎因子水平；同时上调Nrf2/HO-1抗氧化通路，改善氧化应激失衡，并纠正Bcl-2相关X蛋白（Bax）/B细胞淋巴瘤-2（Bcl-2）失衡，抑制半胱天冬氨酸蛋白酶-3（Caspase-3）介导的凋亡过程。结论：TLR4抗体可通过抑制TLR4介导的炎症反应、激活Nrf2/HO-1抗氧化防御并减少细胞凋亡，多通路协同改善PD模型小鼠的神经病理损伤和运动功能障碍。
Abstract:
Objective:To investigate the effects of a Toll-like receptor 4 (TLR4) antibody on motor dysfunction and neuropathological damage in a mouse model of PD,and to elucidate the underlying molecular mechanisms.Methods：A PD mouse model was established using 6-hydroxydopamine and animals were randomly divided into control,PD model,and PD + TLR4 antibody groups.Motor function was evaluated using gait analysis and the open field test.Tyrosine hydroxylase (TH) expression in the substantia nigra was assessed by immunohistochemistry,and neuronal apoptosis was examined using TUNEL staining.Oxidative stress markers and pro-inflammatory cytokines were measured by ELISA.The expression of components of the Toll-like receptor 4 (TLR4)/ TNF receptor-associated factor 6 (TRAF6)/Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathway and apoptosis-related proteins was analyzed by RT-qPCR and Western blotting.Results:Compared with the PD model group,TLR4 antibody intervention significantly improved motor dysfunction in PD mice,increased TH expression in the substantia nigra,and reduced apoptosis.Mechanistically,TLR4 antibody markedly suppressed the activation of TLR4/TRAF6 and downstream nuclear factor-κB (NF-κB) signaling,and decreased the levels of pro-inflammatory factors including interleukin-6 (IL-6),interleukin-1β (IL-1β),and tumor necrosis factor-α (TNF-α).Meanwhile,it upregulated the Nrf2/HO-1 antioxidant pathway,restored oxidative stress imbalance,corrected the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio,and inhibited cysteinyl aspartate-specific protease-3 (Caspase-3)-mediated apoptosis.Conclusion:TLR4 antibody confers neuroprotection in a PD mouse model by attenuating TLR4-mediated neuroinflammation,enhancing Nrf2/HO-1-dependent antioxidant defenses,and suppressing neuronal apoptosis,thereby improving motor dysfunction and neuropathological damage.

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备注/Memo

备注/Memo:
新疆维吾尔自治区自然科学基金青年科学基金资助项目（2023D01C246）
更新日期/Last Update: 2026-07-10