Dihydromyricetin ameliorates depressive-like behaviors in Parkinson’s disease mice by promoting A2 astrocyte polarization and inhibiting neuronal ferroptosis <italic style="font-style: italic">via</italic> suppression of the LCN2/NLRP3 axis

LÜ Menglin; LIU Xiaoqian; ZHANG Baowen; KOU Xianjuan

doi:10.16016/j.2097-0927.202601069

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Dihydromyricetin ameliorates depressive-like behaviors in Parkinson’s disease mice by promoting A2 astrocyte polarization and inhibiting neuronal ferroptosis via suppression of the LCN2/NLRP3 axis

Neuroscience | 更新时间：2026-05-30

- Dihydromyricetin ameliorates depressive-like behaviors in Parkinson’s disease mice by promoting A2 astrocyte polarization and inhibiting neuronal ferroptosis via suppression of the LCN2/NLRP3 axis
- Journal of Army Medical University Vol. 48, Issue 10, Pages: 1339-1352(2026)
- 作者机构：
  
  武汉体育学院运动医学院，湖北武汉
- 作者简介：
  
  KOU Xianjuan， E-mail： kouxianjuan@126.com
- 基金信息：
  
  the Key Project of Natural Science Foundation of Hubei Province(2024AFD242);the Excellent Young and Middle-Aged Science and Technology Innovation Team Program for Higher Education Institutions of Hubei Province(T2024019)
- DOI：10.16016/j.2097-0927.202601069
  CLC： R285.5;R742.5;R749.4
- Received：19 January 2026，
  
  Revised：2026-03-18，
  
  Accepted：21 March 2026，
  
  Published：30 May 2026
- 稿件说明：
移动端阅览
吕梦林，刘小倩，张宝文，等.二氢杨梅素通过抑制LCN2/NLRP3轴促进星形胶质细胞A2型极化抑制神经元铁死亡改善帕金森病小鼠抑郁样行为［J］.陆军军医大学学报，2026，48（10）：1339-1352.DOI：10.16016/j.2097-0927.202601069.

LÜ M L，L X Q，ZHANG B W，et al.Dihydromyricetin ameliorates depressive-like behaviors in Parkinson’s disease mice by promoting A2 astrocyte polarization and inhibiting neuronal ferroptosis via suppression of the LCN2/NLRP3 axis［J］.J Army Med Univ，2026，48（10）：1339-1352.DOI：10.16016/j.2097-0927.202601069.
吕梦林，刘小倩，张宝文，等.二氢杨梅素通过抑制LCN2/NLRP3轴促进星形胶质细胞A2型极化抑制神经元铁死亡改善帕金森病小鼠抑郁样行为［J］.陆军军医大学学报，2026，48（10）：1339-1352.DOI：10.16016/j.2097-0927.202601069. DOI：

LÜ M L，L X Q，ZHANG B W，et al.Dihydromyricetin ameliorates depressive-like behaviors in Parkinson’s disease mice by promoting A2 astrocyte polarization and inhibiting neuronal ferroptosis via suppression of the LCN2/NLRP3 axis［J］.J Army Med Univ，2026，48（10）：1339-1352.DOI：10.16016/j.2097-0927.202601069. DOI：

摘要

目的

抑郁样行为是帕金森病（Parkinson’s disease， PD）中最常见的非运动症状之一，严重影响患者的生活质量。二氢杨梅素（dihydromyricetin， DHM）是一种天然黄酮类化合物，具有一定神经保护作用，但其是否能够改善PD抑郁样行为及其分子机制尚不明确。本研究拟探究DHM改善PD抑郁样行为的潜在作用机制，并筛选和验证其可能调控的关键分子靶点。

方法

将32只7周龄雄性C57BL/6J小鼠［体质量（24.5±1.5） g］按随机数字表法分为4组（

=8）：对照（Control）组、模型（PD）组、阳性对照美多芭干预（PD+Madopar）组和DHM干预（PD+DHM）组。除Control组外，其余各组采用腹腔注射1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-Methyl-4-phenyl-1，2，3，6-tetrahydropyridine hydrochloride， MPTP）建立亚急性PD小鼠模型。采用转棒、爬杆、悬挂实验评估小鼠运动能力，采用开放旷场、强迫游泳、悬尾实验检测小鼠抑郁样行为。基于网络药理学、数据集挖掘和分子对接技术预测DHM治疗PD的关键靶点。利用Western blotting和免疫荧光等技术检测DHM对突触可塑性、星形胶质细胞极化和铁死亡的影响。进一步通过细胞条件培养基实验以验证DHM改善PD抑郁样行为的预测机制。

结果

与PD组相比，PD+DHM组小鼠在转棒实验中的停留时间以及悬挂实验中的支撑时间显著延长（

0.001），爬杆实验中的下杆时间显著缩短（

=0.005 5），旷场实验中的总路程明显增多（

0.001），平均速度加快（

0.001），中心活动距离和活动时间显著增加（

0.01），强迫游泳和悬尾实验中，小鼠的平均不动时间明显缩短（

0.01）。网络药理学和分子对接确定脂质运载蛋白2（lipocalin 2， LCN2）/NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associcated protein 3，NLRP3）轴为DHM的潜在作用靶点。与PD组相比，DHM干预后逆转了神经元的丢失和尼氏小体的减少，并上调了脑源性神经营养因子（brain derived neurotrophic factor， BDNF）、突触蛋白I（synapsin I， SYN1）、突触后密度蛋白95（postsynaptic density 95， PSD95）等突触可塑性指标的表达（

0.01）。DHM干预后LCN2、NLRP3和星形胶质细胞A1型标志物补体C3（complement component 3， C3）的表达与PD组相比均显著下调（

0.001），A2型标志物S100钙结合蛋白A10（S100 calcium binding protein A10， S100A10）的表达显著增加（

0.01）。免疫荧光显示，与PD组相比，PD+DHM组小鼠额叶皮层GFAP/C3阳性细胞数目显著减少而GFAP/S100A10细胞数目显著增加（

0.05）。此外，与PD组相比

，PD+DHM组小鼠额叶皮层组织中酰基辅酶A合成酶长链家族成员4（acyl-CoA synthetase long chain family member 4， ACSL4）、转铁蛋白受体（transferrin receptor， TFRC）表达显著降低（

0.01），GPX4、SLC7A11蛋白的表达显著升高（

0.001）。细胞实验进一步证实DHM及NLRP3抑制剂MCC950预处理的条件培养基逆转了多巴胺能神经元铁死亡相关指标的异常表达（

0.01）。

结论

DHM可能通过抑制LCN2/NLRP3轴促进星形胶质细胞向A2型极化，缓解星形胶质细胞极化失衡与神经元铁死亡，进而改善PD小鼠抑郁样行为。

Abstract

Objective

Depressive-like behaviors is one of the most prevalent non-motor symptoms in Parkinson’s disease (PD)

severely compromising patients’ quality of life. Dihydromyricetin (DHM)

a natural flavonoid

exhibits neuroprotective effects

but its ability to ameliorate PD-related depressive-like behaviors and the underlying mechanisms remain unclear. This study aimed to investigate DHM’s mechanism for improving depressive-like behaviors in PD and identify its key molecular targets.

Methods

Thirty-two 7 weeks old male C57BL/6J mice (weighting 24.5±1.5 g) were randomly divided into 4 groups (

=8): Control

PD model

PD+Madopar (positive control)

and PD+DHM. Except the control group

all groups received intraperitoneal 1-methyl-4-phenyl-1

6-tetrahydropyridine (MPTP) to establish subacute PD models. Motor function was assessed

via

rotarod

pole and wire hang tests; depressive-like behaviors were evaluated using the open field

forced swimming

and tail suspension tests. Network pharmacology

dataset mining

and molecular docking predicted DHM’s key targets for PD treatment. Western blotting and immunofluorescence detected DHM’s effects on synaptic plasticity

astrocyte polarization

and ferroptosis. Conditioned medium experiments further validated the predicted mechanisms.

Results

Compared with the PD group

PD+DHM mice showed significantly prolonged rotarod duration and suspension time (

0.001)

reduced p

ole descent time (

=0.005 5)

increased total distance (

0.001) and velocity (

0.001) in open field test

with higher central activity distance/time ratios (

0.01)

and shorter immobility times in forced swimming and suspension tests (

0.01). Network pharmacology and molecular docking identified the Lipocalin-2 (LCN2)/NOD-like receptor thermal protein domain associcated protein 3（NLRP3) axis as DHM’s potential target. DHM intervention reversed neuronal loss and Nissl body reduction while upregulating synaptic plasticity markers BDNF

SYN1 and PSD95

compared with the PD group (

0.01). DHM significantly downregulated LCN2

NLRP3

and A1-astrocyte marker complement component 3 (C3;

0.001)

but upregulated A2-marker S100 calcium binding protein A10（S100A10;

0.01). Compared with the PD gruop

immunofluorescence revealed reduced GFAP/C3-positive cells and increased GFAP/S100A10 cells in the prefrontal cortex of PD+DHM group (

0.05). Additionally

DHM decreased acyl-CoA synthetase long chain family member 4 (ACSL4) and Transferrin receptor (TFRC) expression (

0.001)

while increasing GPX4 and SLC7A11 levels (

0.001) in the prefrontal cortex. Conditioned medium experiments confirmed that DHM and NLRP3 inhibitor MCC950 reversed abnormal ferroptosis-related changes in dopaminergic neurons (

0.01).

Conclusion

DHM may ameliorate depressive-like behaviors in PD mice by inhibiting the LCN2/NLRP3 axis which promotes A2-astrocyte polarization

mitigates imbalance in astrocyte polarization and alleviates neuronal ferroptosis.

关键词

Keywords

references

SU D N ， CUI Y S ， HE C Z ， et al . Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050： modelling study of Global Burden of Disease Study 2021 ［J］. BMJ ， 2025 ， 388 ： e080952 . DOI： 10.1136/bmj-2024-080952 http://dx.doi.org/10.1136/bmj-2024-080952 .

ARMSTRONG M J ， OKUN M S . Diagnosis and treatment of Parkinson disease： a review ［J］. JAMA ， 2020 ， 323 （ 6 ）： 548 - 560 . DOI： 10.1001/jama.2019.22360 http://dx.doi.org/10.1001/jama.2019.22360 .

李静，胡晓飞，周振华 . 帕金森病运动亚型患者运动症状及认知功能进展特征： 3年纵向研究［J］. 第三军医大学学报， 2020 ， 42 （ 13 ）： 1273 - 1278 . DOI： 10.16016/j.1000-5404.202001202 http://dx.doi.org/10.16016/j.1000-5404.202001202 .

LI J ， HU X F ， ZHOU Z H . Progression characteristics of motor symptoms and cognitive function in patients with motor subtype of Parkinson’s disease： a 3-year longitudinal study ［J］. J Third Mil Med Univ ， 2020 ， 42 （ 13 ）： 1273 - 1278 . DOI： 10.16016/j.1000-5404.202001202 http://dx.doi.org/10.16016/j.1000-5404.202001202 .

GALLAGHER D A ， LEES A J ， SCHRAG A . What are the most important nonmotor symptoms in patients with Parkinson’s disease and are we missing them？［J］. Mov Disord ， 2010 ， 25 （ 15 ）： 2493 - 2500 . DOI： 10.1002/mds.23394 http://dx.doi.org/10.1002/mds.23394 .

PRANGE S ， KLINGER H ， LAURENCIN C ， et al . Depression in patients with Parkinson’s disease： current understanding of its neurobiology and implications for treatment ［J］. Drugs Aging ， 2022 ， 39 （ 6 ）： 417 - 439 . DOI： 10.1007/s40266-022-00942-1 http://dx.doi.org/10.1007/s40266-022-00942-1 .

KRITZINGER C ， VOLLSTEDT E J ， HÜCKELHEIM K ， et al . Qualitative characteristics of depression in Parkinson’s patients and controls ［J］. Behav Neurol ， 2015 ， 2015 ： 961372 . DOI： 10.1155/2015/961372 http://dx.doi.org/10.1155/2015/961372 .

XIAO Z X ， WANG X Y ， PAN X N ， et al . Mitochondrial iron dyshomeostasis and its potential as a therapeutic target for Parkinson’s disease ［J］. Exp Neurol ， 2024 ， 372 ： 114614 . DOI： 10.1016/j.expneurol.2023.114614 http://dx.doi.org/10.1016/j.expneurol.2023.114614 .

MANISCALCHI A ， BENZI JUNCOS O N ， CONDE M A ， et al . New insights on neurodegeneration triggered by iron accumulation： Intersections with neutral lipid metabolism， ferroptosis， and motor impairment ［J］. Redox Biol ， 2024 ， 71 ： 103074 . DOI： 10.1016/j.redox.2024.103074 http://dx.doi.org/10.1016/j.redox.2024.103074 .

ZHOU M H ， XU K Y ， GE J X ， et al . Targeting ferroptosis in Parkinson’s disease： mechanisms and emerging therapeutic strategies ［J］. Int J Mol Sci ， 2024 ， 25 （ 23 ）： 13042 . DOI： 10.3390/ijms252313042 http://dx.doi.org/10.3390/ijms252313042 .

CHEN Y ， ZHENG Y Y ， CHEN R X ， et al . Dihydromyricetin attenuates diabetic cardiomyopathy by inhibiting oxidative stress， inflammation and necroptosis via sirtuin 3 activation ［J］. Antioxidants ， 2023 ， 12 （ 1 ）： 200 . DOI： 10.3390/antiox12010200 http://dx.doi.org/10.3390/antiox12010200 .

KOU X J ， LI J ， BIAN J ， et al . Ampelopsin attenuates 6-OHDA-induced neurotoxicity by regulating GSK-3β/NRF2/ARE signalling ［J］. J Funct Foods ， 2015 ， 19 ： 765 - 774 . DOI： 10.1016/j.jff.2015.10.010 http://dx.doi.org/10.1016/j.jff.2015.10.010 .

童诗逸，张蒙，盛科研，等 . 二氢杨梅素抑制坏死性凋亡信号通路改善帕金森病小鼠认知功能障碍的作用机制［J］. 中药新药与临床药理， 2023 ， 34 （ 3 ）： 296 - 302 . DOI： 10.19378/j.issn.1003-9783.2023.03.002 http://dx.doi.org/10.19378/j.issn.1003-9783.2023.03.002 .

TONG S Y ， ZHANG M ， SHENG K Y ， et al . Mechanisms of dihydromyricetin mediated necroptosis signaling pathway in improving cognitive dysfunction in mice with Parkinson’s disease ［J］. Tradit Chin Drug Res Clin Pharmacol ， 2023 ， 34 （ 3 ）： 296 - 302 . DOI： 10.19378/j.issn.1003-9783.2023.03.002 http://dx.doi.org/10.19378/j.issn.1003-9783.2023.03.002 .

张蒙，张源源，牛梦竹，等 . 双氢杨梅素通过诱导自噬减轻慢性帕金森病小鼠的细胞焦亡和坏死性凋亡［J］. 南方医科大学学报， 2023 ， 43 （ 8 ）： 1268 - 1278 . DOI： 10.12122/j.issn.1673-4254.2023.08.02 http://dx.doi.org/10.12122/j.issn.1673-4254.2023.08.02 .

ZHANG M ， ZHANG Y Y ， NIU M Z ， et al . Dihydromyricetin alleviates pyroptosis and necroptosis in mice with MPTP-induced chronic Parkinson’s disease by inducing autophagy ［J］. J South Med Univ ， 2023 ， 43 （ 8 ）： 1268 - 1278 . DOI： 10.12122/j.issn.1673-4254.2023.08.02 http://dx.doi.org/10.12122/j.issn.1673-4254.2023.08.02 .

XIE J B ， ZHANG T T ， LI P C ， et al . Dihydromyricetin attenuates cerebral ischemia reperfusion injury by inhibiting SPHK1/mTOR signaling and targeting ferroptosis ［J］. Drug Des Devel Ther ， 2022 ， 16 ： 3071 - 3085 . DOI： 10.2147/DDDT.S378786 http://dx.doi.org/10.2147/DDDT.S378786 .

XU Z M ， ZHANG M J ， WANG W W ， et al . Dihydromyricetin attenuates cisplatin-induced acute kidney injury by reducing oxidative stress， inflammation and ferroptosis ［J］. Toxicol Appl Pharmacol ， 2023 ， 473 ： 116595 . DOI： 10.1016/j.taap.2023.116595 http://dx.doi.org/10.1016/j.taap.2023.116595 .

ZHANG Q S ， HENG Y ， MOU Z ， et al . Reassessment of subacute MPTP-treated mice as animal model of Parkinson’s disease ［J］. Acta Pharmacol Sin ， 2017 ， 38 （ 10 ）： 1317 - 1328 . DOI： 10.1038/aps.2017.49 http://dx.doi.org/10.1038/aps.2017.49 .

张宝文，吕梦林，陈丹丹，等 . 40 Hz光闪烁刺激调节NAD + /Sirt1/PGC-1α信号通路对帕金森病伴抑郁小鼠的影响［J］. 中国激光， 2025 ， 52 （ 15 ）： 113 - 125 . DOI： 10.3788/CJL250452 http://dx.doi.org/10.3788/CJL250452 .

ZHANG B W ， LYU M L ， CHEN D D ， et al . Effects of 40 Hz light flicker stimulation on NAD + /Sirt1/PGC-1α signaling pathway in Parkinson’s disease with depression mice ［J］. Chin J Lasers ， 2025 ， 52 （ 15 ）： 113 - 125 . DOI： 10.3788/CJL250452 http://dx.doi.org/10.3788/CJL250452 .

REN Z X ， ZHAO Y F ， CAO T ， et al . Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson’s disease by suppressing glycogen synthase kinase-3 beta activity ［J］. Acta Pharmacol Sin ， 2016 ， 37 （ 10 ）： 1315 - 1324 . DOI： 10.1038/aps.2016.42 http://dx.doi.org/10.1038/aps.2016.42 .

JIANG S Y ， TIAN T ， YAO H ， et al . The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson’s disease via LCN2-dependent astrocyte senescence ［J］. Cell Death Differ ， 2023 ， 30 （ 10 ）： 2280 - 2292 . DOI： 10.1038/s41418-023-01216-y http://dx.doi.org/10.1038/s41418-023-01216-y .

刘醒然，牛梦竹，高原，等 . 二氢杨梅素改善糖尿病肾病的关键靶分子的筛选与验证［J］. 陆军军医大学学报， 2025 ， 47 （ 21 ）： 2663 - 2677 . DOI： 10.16016/j.2097-0927.202507095 http://dx.doi.org/10.16016/j.2097-0927.202507095 .

LIU X R ， NIU M Z ， GAO Y ， et al . Screening and validation of key molecular targets for dihydromyricetin in ameliorating diabetic nephropathy ［J］. J Army Med Univ ， 2025 ， 47 （ 21 ）： 2663 - 2677 . DOI： 10.16016/j.2097-0927.202507095 http://dx.doi.org/10.16016/j.2097-0927.202507095 .

BASHIR B ， VISHWAS S ， GUPTA G ， et al . Does drug repurposing bridge the gaps in management of Parkinson’s disease？ Unravelling the facts and fallacies ［J］. Ageing Res Rev ， 2025 ， 105 ： 102693 . DOI： 10.1016/j.arr.2025.102693 http://dx.doi.org/10.1016/j.arr.2025.102693 .

KIM J H ， YOON H J ， CHOI Y ， et al . 6-Shogaol， a neuro-nutraceutical derived from ginger， alleviates motor symptoms and depression-like behaviors and modulates the release of monoamine neurotransmitters in Parkinson’s disease mice ［J］. Eur J Nutr ， 2025 ， 64 （ 3 ）： 116 . DOI： 10.1007/s00394-025-03639-4 http://dx.doi.org/10.1007/s00394-025-03639-4 .

郑淇，徐晓敏，王思萌，等 . 中医药在帕金森病与抑郁共病中的作用机制研究进展［J］. 中国实验方剂学杂志， 2026 ， 32 （ 4 ）： 268 - 276 . DOI： 10.13422/j.cnki.syfjx.20251902 http://dx.doi.org/10.13422/j.cnki.syfjx.20251902 .

ZHENG Q ， XU X M ， WANG S M ， et al . Mechanism of traditional Chinese medicine in comorbidity of Parkinson’s disease and depression： a review ［J］. Chin J Exp Tradit Med Formulae ， 2026 ， 32 （ 4 ）： 268 - 276 . DOI： 10.13422/j.cnki.syfjx.20251902 http://dx.doi.org/10.13422/j.cnki.syfjx.20251902 .

FELDMANN A ， ILLES Z ， KOSZTOLANYI P ， et al . Morphometric changes of gray matter in Parkinson’s disease with depression： a voxel-based morphometry study ［J］. Mov Disord ， 2008 ， 23 （ 1 ）： 42 - 46 . DOI： 10.1002/mds.21765 http://dx.doi.org/10.1002/mds.21765 .

BROWNE C A ， HAMMACK R ， LUCKI I . Dysregulation of the lateral habenula in major depressive disorder ［J］. Front Synaptic Neurosci ， 2018 ， 10 ： 46 . DOI： 10.3389/fnsyn. 2018. 00046 http://dx.doi.org/10.3389/fnsyn.2018.00046 .

LUO X F ， ZHANG B L ， LI J C ， et al . Lateral habenula as a link between dopaminergic and serotonergic systems contributes to depressive symptoms in Parkinson’s disease ［J］. Brain Res Bull ， 2015 ， 110 ： 40 - 46 . DOI： 10.1016/j.brainresbull.2014.11.006 http://dx.doi.org/10.1016/j.brainresbull.2014.11.006 .

MIQUEL RIO L ， JERICÓ ESCOLAR J ， SARRIÉS SERRANO U ， et al . Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype ［J］. npj Park Dis ， 2025 ， 11 ： 242 . DOI： 10.1038/s41531-025-01073-1 http://dx.doi.org/10.1038/s41531-025-01073-1 .

FAN Y Y ， LI X H ， MA J J ， et al . Increased plasma lipocalin-2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson’s disease ［J］. J Neurosci Res ， 2024 ， 102 （ 2 ）： e25303 . DOI： 10.1002/jnr.25303 http://dx.doi.org/10.1002/jnr.25303 .

JIAO Y Y ， TIAN T ， ZHU Z ， et al . Extracellular LCN2 binding to 24p3R in astrocytes impedes α-synuclein endocytosis in Parkinson’s disease ［J］. Adv Sci ， 2025 ， 12 （ 39 ）： e01694 . DOI： 10.1002/advs.202501694 http://dx.doi.org/10.1002/advs.202501694 .

TAN Q Q ， ZHANG C X ， RAO X Q ， et al . The interaction of lipocalin-2 and astrocytes in neuroinflammation： mechanisms and therapeutic application ［J］. Front Immunol ， 2024 ， 15 ： 1358719 . DOI： 10.3389/fimmu. 2024. 1358719 http://dx.doi.org/10.3389/fimmu.2024.1358719 .

LI J J ， XU P F ， HONG Y ， et al . Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury ［J］. J Neuroinflammation ， 2023 ， 20 （ 1 ）： 148 . DOI： 10.1186/s12974-023-02819-5 http://dx.doi.org/10.1186/s12974-023-02819-5 .

WEN Y Y ， ZHAO C L ， CHEN J ， et al . Gandouling regulates ferroptosis and improves neuroinflammation in Wilson’s disease through the LCN2/NLRP3 signaling pathway ［J］. J Inflamm Res ， 2024 ， 17 ： 5599 - 5618 . DOI： 10.2147/JIR.S465341 http://dx.doi.org/10.2147/JIR.S465341 .

ZHANG L S ， XU Z Z ， JIA Z H ， et al . Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration ［J］. Nat Aging ， 2025 ， 5 （ 3 ）： 468 - 485 . DOI： 10.1038/s43587-024-00792-z http://dx.doi.org/10.1038/s43587-024-00792-z .

CHOI I ， CHOI D J ， YANG H J ， et al . PINK1 expression increases during brain development and stem cell differentiation， and affects the development of GFAP-positive astrocytes ［J］. Mol Brain ， 2016 ， 9 ： 5 . DOI： 10.1186/s13041-016-0186-6 http://dx.doi.org/10.1186/s13041-016-0186-6 .

WANG H Q ， WU S ， JIANG X D ， et al . Acteoside alleviates salsolinol-induced Parkinson’s disease by inhibiting ferroptosis via activating Nrf2/SLC7A11/GPX4 pathway ［J］. Exp Neurol ， 2025 ， 385 ： 115084 . DOI： 10.1016/j.expneurol. 2024.115084 http://dx.doi.org/10.1016/j.expneurol.2024.115084 .

黄丽平，邓敏贞，冯真英，等 . 石菖蒲新苯丙素类化合物HDDM对帕金森病小鼠多巴胺能神经元的保护机制［J］. 中药新药与临床药理， 2025 ， 36 （ 9 ）： 1483 - 1491 . DOI： 10.19378/j.issn.1003-9783.2025.09.008 http://dx.doi.org/10.19378/j.issn.1003-9783.2025.09.008 .

HUANG L P ， DENG M Z ， FENG Z Y ， et al . Neuroprotective mechanism of acori tatarinowii rhizoma-derived novel phenylpropanoids HDDM on dopaminergic neurons in Parkinson’s disease mice ［J］. Tradit Chin Drug Res Clin Pharmacol ， 2025 ， 36 （ 9 ）： 1483 - 1491 . DOI： 10.19378/j.issn.1003-9783.2025.09.008 http://dx.doi.org/10.19378/j.issn.1003-9783.2025.09.008 .

DOLL S ， PRONETH B ， TYURINA Y Y ， et al . ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition ［J］. Nat Chem Biol ， 2017 ， 13 （ 1 ）： 91 - 98 . DOI： 10.1038/nchembio.2239 http://dx.doi.org/10.1038/nchembio.2239 .

SHCHEPINOV M S ， CHOU V P ， POLLOCK E ， et al . Isotopic reinforcement of essential polyunsaturated fatty acids diminishes nigrostriatal degeneration in a mouse model of Parkinson’s disease ［J］. Toxicol Lett ， 2011 ， 207 （ 2 ）： 97 - 103 . DOI： 10.1016/j.toxlet.2011.07.020 http://dx.doi.org/10.1016/j.toxlet.2011.07.020 .

万钰铃，陈彦君，陈静文，等 . 帕宁Ⅰ号方对帕金森病小鼠多巴胺能神经元氧化应激介导的铁死亡途径的影响［J］. 上海中医药杂志， 2024 ， 58 （ 9 ）： 80 - 90 . DOI： 10.16305/j.1007-1334.2024.2312042 http://dx.doi.org/10.16305/j.1007-1334.2024.2312042 .

WAN Y L ， CHEN Y J ， CHEN J W ， et al . Effects of Paning Ⅰ formula on oxidative stress-mediated ferroptosis pathway in dopaminergic neurons of PD mice ［J］. Shanghai J Tradit Chin Med ， 2024 ， 58 （ 9 ）： 80 - 90 . DOI： 10.16305/j.1007-1334.2024.2312042 http://dx.doi.org/10.16305/j.1007-1334.2024.2312042 .

PYATIGORSKAYA N ， SHARMAN M ， CORVOL J C ， et al . High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry ［J］. Mov Disord ， 2015 ， 30 （ 8 ）： 1077 - 1084 . DOI： 10.1002/mds.26218 http://dx.doi.org/10.1002/mds.26218 .

STOCKWELL B R ， FRIEDMANN ANGELI J P ， BAYIR H ， et al . Ferroptosis： a regulated cell death nexus linking metabolism， redox biology， and disease ［J］. Cell ， 2017 ， 171 （ 2 ）： 273 - 285 . DOI： 10.1016/j.cell.2017.09.021 http://dx.doi.org/10.1016/j.cell.2017.09.021 .

WONG M ， AHMED A ， LUO W J ， et al . Combined manganese-iron exposure reduced oxidative stress is associated with the NRF2/NQO1 pathway in astrocytic C8-D1A cells ［J］. Biol Trace Elem Res ， 2026 ， 204 （ 2 ）： 786 - 802 . DOI： 10.1007/s12011-025-04708-9 http://dx.doi.org/10.1007/s12011-025-04708-9 .

ISHII T ， WARABI E ， MANN G E . Circadian control of BDNF-mediated Nrf2 activation in astrocytes protects dopaminergic neurons from ferroptosis ［J］. Free Radic Biol Med ， 2019 ， 133 ： 169 - 178 . DOI： 10.1016/j.freeradbiomed. 2018. 09.002 http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.002 .

SCHIPPER H M ， SONG W ， TAVITIAN A ， et al . The sinister face of heme oxygenase-1 in brain aging and disease ［J］. Prog Neurobiol ， 2019 ， 172 ： 40 - 70 . DOI： 10.1016/j.pneurobio.2018.06.008 http://dx.doi.org/10.1016/j.pneurobio.2018.06.008 .

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DOI：10.16016/j.2097-0927.202601069

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