收稿日期: 2025-07-04
网络出版日期: 2025-11-26
基金资助
广东省基础与应用基础研究基金项目(2025A1515010578);广东省医学科学技术研究基金项目(B2023087);深圳市科技计划项目(JCYJ20220530150212028);深圳市“医疗卫生三名工程”项目资助项目(SZZYSM202106009)
The comparison of ferroptosis characteristics and motor deficits in Parkinson′s disease mouse models
Received date: 2025-07-04
Online published: 2025-11-26
目的 比较不同帕金森病（PD）小鼠模型铁死亡特征及运动功能障碍差异。 方法 通过动物行为学观察、病理切片、蛋白检测、脂质过氧化和氧化应激检测，分析对照（Control）组、假手术（Sham）组、六羟基多巴胺（6-OHDA）组、1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）组、脂多糖（LPS）组PD动物模型的铁死亡特征和运动功能障碍差异。 结果 3组模型患侧黑质TH阳性神经元数量均减少，神经元变性且尼氏小体减少。在行为学检测中，6-OHDA组出现最显著运动障碍；在黑质中，6-OHDA组、LPS组和MPTP组的FTH1蛋白表达量均显著下降（P < 0.01，P < 0.05，P < 0.01）；GPX4表达下降（P < 0.001，P < 0.001，P < 0.01）。6-OHDA组和MPTP组的丙二醛（MDA）含量表达升高（P < 0.05，P < 0.05）；谷胱甘肽（GSH）检测见6-OHDA组、MPTP组和LPS组表达下降（P < 0.01，P < 0.001，P < 0.001）；活性氧（ROS）检测见MPTP组和LPS组表达上升（P < 0.05，P < 0.05）。 结论 6-OHDA模型适合PD行为学及运动症状机制研究；MPTP模型适用于铁死亡通路研究；LPS模型可作为神经炎症机制研究的补充。
黎海燕 , 李萌竹 , 陈孟璇 , 高达 , 段可欣 , 赵丽君 , 朱美玲 . 帕金森病小鼠动物模型铁死亡特征及运动障碍差异比较[J]. 实用医学杂志, 2025 , 41(22) : 3501 -3509 . DOI: 10.3969/j.issn.1006-5725.2025.22.006
Objective To compare ferroptosis characteristics and motor dysfunction across different mouse models of Parkinson′s disease （PD）. Methods Animal models of PD were divided into five groups： the control group， sham-operated group， 6-hydroxydopamine （6-OHDA） group， 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） group， and lipopolysaccharide （LPS） group. Differences in ferroptosis-related features and motor dysfunction across these groups were evaluated through behavioral observation， histopathological examination， protein analysis， and assessment of lipid peroxidation and oxidative stress levels. Results In all three model groups， the number of TH-positive neurons in the substantia nigra on the lesioned side was significantly reduced， accompanied by evident neuronal degeneration and a marked decrease in Nissl bodies. Behavioral assessments revealed that the 6-OHDA group displayed the most severe motor deficits. In the substantia nigra， FTH1 protein expression was significantly downregulated in the 6-OHDA， LPS， and MPTP groups （P < 0.01， P < 0.05， P < 0.01）， respectively， while GPX4 expression was also reduced （P < 0.001， P < 0.001， P < 0.01）. Malondialdehyde （MDA） levels were significantly elevated in both the 6-OHDA and MPTP groups （P < 0.05， P < 0.05）. Glutathione （GSH） assays demonstrated markedly reduced levels in the 6-OHDA， MPTP， and LPS groups （P < 0.01， P < 0.001， P < 0.001）. Reactive oxygen species （ROS） detection revealed a significant increase in the MPTP and LPS groups （P < 0.05， P < 0.05）. Conclusion The 6-OHDA model is well suited for studying PD-related behaviors and the underlying mechanisms of motor symptoms， the MPTP model is particularly effective for investigating the ferroptosis pathway， and the LPS model serves as a valuable complement for research on neuroinflammation mechanisms.
Key words： Parkinson′s disease; ferroptosis; 6-OHDA; MPTP; LPS; animal model
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