帕金森病小鼠动物模型铁死亡特征及运动障碍差异比较

doi:10.3969/j.issn.1006-5725.2025.22.006

Abstract

Abstract:

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

CLC Number:

Q95-33

Haiyan LI,Mengzhu LI,Mengxuan CHEN,Da GAO,Kexin DUAN,Lijun ZHAO,Meiling ZHU. The comparison of ferroptosis characteristics and motor deficits in Parkinson′s disease mouse models[J]. The Journal of Practical Medicine, 2025, 41(22): 3501-3509.

Figures/Tables 10

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References 29

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组别	每分钟旋转圈数
Control组	1.44 ± 1.13
Sham-6-OHDA组	1.11 ± 0.78
6-OHDA组	8.89 ± 1.83^?#
F值	99.45
P值	< 0.001

组别	转棒停留时间/s	旷场运动总路程/cm	旷场运动速度/（cm/s）
Control组	300.00（184.50，300.00）	583.10 ± 156.30	1.63 ± 0.40
Sham-6-OHDA组	277.00（243.00，300.00）	469.40 ± 67.19	1.57 ± 0.23
6-OHDA组	23.00（14.50，68.50）^be	326.80 ± 85.54^cf	1.08 ± 0.29^adf
Sham-MPTP组	278.00（216.00，300.00）	521.90 ± 98.63	1.76 ± 0.34
MPTP组	27.00（8.50，56.50）^be	475.40 ± 93.15	1.57 ± 0.31^fg
Sham-LPS组	262.00（233.00，299.00）	495.60 ± 70.02	1.67 ± 0.24
LPS组	15.00（5.50，52.50）^be	582.60 ± 152.50	2.26 ± 0.39^be
F/H值	44.47	5.77	10.73
P值	< 0.001	< 0.001	< 0.001

组别	TFR	ACSL4	TH	SLC7A11	FTH1	GPX4
Control组	1.00	1.00	1.00	1.00	1.00	1.00
Sham-6-OHDA组	0.87 ± 0.17	1.07 ± 0.09	0.89 ± 0.06	1.03 ± 0.09	1.00 ± 0.05	1.06 ± 0.05
6-OHDA组	1.63 ± 0.19^ac	1.23 ± 0.39	0.15 ± 0.03^be	0.69 ± 0.03^c	0.71 ± 0.12^ad	0.76 ± 0.01^be
Sham-MPTP组	0.97 ± 0.19	1.10 ± 0.06	0.84 ± 0.02	1.01 ± 0.13	0.98 ± 0.13	0.90 ± 0.07
MPTP组	1.50 ± 0.20	1.71 ± 0.38^ac	0.50 ± 0.05^bd	0.64 ± 0.23^ac	0.74 ± 0.11^ac	0.61 ± 0.02^bef
Sham-LPS组	1.14 ± 0.21	0.89 ± 0.04	0.91 ± 0.18	1.12 ± 0.07	1.07 ± 0.03	0.88 ± 0.06
LPS组	1.13 ± 0.37	1.57 ± 0.06^c	0.41 ± 0.13^be	0.81 ± 0.02	0.72 ± 0.05^ad	0.71 ± 0.04^bd
F值	5.13	6.22	37.73	8.52	10.75	41.33
P值	< 0.01	< 0.01	< 0.001	< 0.001	< 0.001	< 0.001

组别	TFR	ACSL4	TH	SLC7A11	FTH1	GPX4
Control组	1.00	1.00	1.00	1.00	1.00	1.00
Sham-6-OHDA组	1.00 ± 0.07	0.82 ± 0.06	0.96 ± 0.03	0.94 ± 0.07	0.98 ± 0.20	0.95 ± 0.04
6-OHDA组	1.42 ± 0.10^ad	1.71 ± 0.12^cf	0.71 ± 0.05^ce	0.69 ± 0.08^bd	0.55 ± 0.03^ce	0.62 ± 0.03^cf
Sham-MPTP组	1.09 ± 0.07	1.30 ± 0.90	1.12 ± 0.12	1.00 ± 0.14	0.92 ± 0.05	1.05 ± 0.06
MPTP组	1.44 ± 0.90^bd	1.85 ± 0.12^ce	0.56 ± 0.02^cfh	0.74 ± 0.01^aeg	0.54 ± 0.13^ce	0.75 ± 0.12^be
Sham-LPS组	1.02 ± 0.18	1.05 ± 0.18	1.05 ± 0.07	0.86 ± 0.09	0.96 ± 0.01	1.05 ± 0.07
LPS组	1.53 ± 0.22^be	1.78 ± 0.25^cf	0.81 ± 0.05^ae	0.49 ± 0.04^cf	0.61 ± 0.01^be	0.76 ± 0.10^ae
F值	11.07	26.87	33.52	19.66	16.15	18.01
P值	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

组别	MDA/（nmol/g）	GSH/（μmol/L）
Control组	503.10 ± 111.40	0.92 ± 0.06
6-OHDA组	747.60 ± 37.64^a	0.45 ± 0.11^b
MPTP组	759.20 ± 64.98^a	0.07 ± 0.07^cd
LPS组	600.20 ± 96.67	0.21 ± 0.14^c
F值	6.64	42.12
P值	< 0.05	< 0.001

The comparison of ferroptosis characteristics and motor deficits in Parkinson′s disease mouse models

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