| 30 | 0 | 15 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探究普拉克索对帕金森病(PD)小鼠多巴胺能神经元变性死亡及肌醇需求酶1(IRE1α)/X盒结合蛋白(XBP)-1通路的影响。方法 75只小鼠随机分为对照(Control)组、模型(PD)组、低、高剂量普拉克索(PPX-low、-high)组，IRE1α/XBP-1通路抑制剂(MKC8866)组各15只。采用连续7 d腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,30 mg/kg)制备PD小鼠模型，PPX-low、-high组、MKC8866组腹腔注射普拉克索(0.25、0.50 mg/kg)和MKC8866(150 mg/kg),Control组、PD组腹腔注射等量生理盐水，连续注射3 w后进行行为学检测；苏木素-伊红(HE)染色、尼氏染色检测中脑组织、黑质区、纹状体区神经元损伤；免疫组化染色、实时荧光定量聚合酶链式反应(RT-qPCR)、Western印迹检测中脑组织、黑质区、纹状体区酪氨酸羟化酶(TH)、突触核蛋白-α(α-syn)、葡萄糖调节蛋白(GRP)78、C/EBP家族同源蛋白(CHOP)、IRE1α、XBP-1表达。结果 与Control组相比，PD组运动功能降低，黑质区和纹状体区多巴胺能神经元数量减少，中脑组织TH表达降低，α-syn表达升高，GRP78、CHOP、XBP-1 mRNA和蛋白、IRE1α mRNA和p-IRE1α/IRE1α蛋白表达升高，差异显著(P<0.05);与PD组相比，PPX-low、-high组、MKC8866组运动功能提高，黑质区和纹状体区多巴胺能神经元数量增多，中脑组织TH表达升高，α-syn表达降低，GRP78、CHOP、XBP-1 mRNA和蛋白、IRE1α mRNA和p-IRE1α/IRE1α蛋白表达降低，差异显著(P<0.05)。结论 普拉克索能够改善PD小鼠运动功能，抑制多巴胺能神经元变性死亡，其可能通过调控IRE1α/XBP-1通路抑制内质网应激而发挥作用。
Abstract：1 Costa HN,Esteves AR,Empadinhas N,et al.Parkinson′s disease:a multisystem disorder[J].Neurosci Bull,2023;39(1):113-24.
2 Kamath T,Abdulraouf A,Burris SJ,et al.Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson′s disease[J].Nat Neurosci,2022;25(5):588-95.
3 Lima IS,Pêgo AC,Barros JT,et al.Cell death-osis of dopaminergic neurons and the role of iron in Parkinson′s disease[J].Antioxid Redox Signal,2021;35(6):453-73.
4 Li DW,Qi XD,Zhang CH,et al.Annexin A2 degradation contributes to dopaminergic cell apoptosis via regulating p53 in neurodegenerative conditions[J].Neuroreport,2021;32(15):1263-8.
5 Anerillas C,Mazan-Mamczarz K,Herman AB,et al.The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress[J].Nat Aging,2023;3(10):1237-50.
6 Li BX,Yang H,Wu HP,et al.Hydroquinone-induced endoplasmic reticulum stress affects TK6 cell autophagy and apoptosis via ATF6-mTOR[J].Environ Toxicol,2023;38(8):1874-90.
7 Meng MJ,Zhao X,Huo R,et al.Disodium fumarate alleviates endoplasmic reticulum stress,mitochondrial damage,and oxidative stress induced by the high-concentrate diet in the mammary gland tissue of hu sheep[J].Antioxidants(Basel),2023;12(2):223.
8 Chern YJ,Wong JCT,Cheng GSW,et al.The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer[J].Cell Death Dis,2019;10(7):504.
9 郑佳音，杨璇，王昕宇，等.内质网应激IRE1α/XBP-1通路在多巴胺能神经元变性死亡中的作用[J].脑与神经疾病杂志，2024;32(2):67-71.
10 宁百乐，张芹欣，邓敏贞，等.补肾开窍方通过抑制IRE1/XBP1内质网应激通路发挥对帕金森病模型大鼠的神经保护作用[J].广州中医药大学学报，2019;36(4):549-55.
11 Gencler OS,Oztekin N,Oztekin MF.Comparison of pramipexole versus ropinirole in the treatment of Parkinson′s disease[J].Ideggyogy Sz,2022;75:39-49.
12 Hauser RA,Giladi N,Poewe W,et al.P2B001(extended release pramipexole and rasagiline):a new treatment option in development for Parkinson′s disease[J].Adv Ther,2022;39(5):1881-94.
13 Inden M,Kitamura Y,Tamaki A,et al.Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice[J].Neurochem Int,2009;55(8):760-7.
14 Dong AQ,Yang YP,Jiang SM,et al.Pramipexole inhibits astrocytic NLRP3 inflammasome activation via Drd3-dependent autophagy in a mouse model of Parkinson′s disease[J].Acta Pharmacol Sin,2023;44(1):32-43.
15 Lima IS,Pêgo AC,Barros JT,et al.Cell death-osis of dopaminergic neurons and the role of iron in Parkinson′s disease[J].Antioxid Redox Signal,2021;35(6):453-73.
16 Amo-Aparicio J,Daly J,H⌀jen JF,et al.Pharmacologic inhibition of NLRP3 reduces the levels of α-synuclein and protects dopaminergic neurons in a model of Parkinson′s disease[J].J Neuroinflamm,2023;20(1):147.
17 Soileau LG,Talbot NC,Storey NR,et al.Impulse control disorders in Parkinson′s disease patients treated with pramipexole and ropinirole:a systematic review and meta-analysis[J].Neurol Sci,2024;45(4):1399-408.
18 魏冉，张亚丽.普拉克索在帕金森病患者中疗效及预后的研究进展[J].内蒙古医科大学学报，2023;45(6):666-9.
19 Rausch WD,Wang F,Radad K.From the tyrosine hydroxylase hypothesis of Parkinson′s disease to modern strategies:a short historical overview[J].J Neural Transm(Vienna),2022;129(5-6):487-95.
20 Giri B,Seamon M,Banerjee A,et al.Emerging urinary alpha-synuclein and miRNA biomarkers in Parkinson′s disease[J].Metab Brain Dis,2022;37(6):1687-96.
21 李莉莉，利慧华，贾亚楠，等.内质网应激在帕金森病发病机制中的研究进展[J].基因组学与应用生物学，2017;36(2):523-30.
22 朱宝平，于丹丹，曾聪慧，等.牡荆素调控PERK-CHOP内质网应激途径对帕金森病模型小鼠神经功能的改善作用研究[J].国际检验医学杂志，2024;45(9):1037-43.
23 Chern YJ,Wong JCT,Cheng GSW,et al.The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer[J].Cell Death Dis,2019;10(7):504.
24 Al Zaidi M,Marggraf V,Repges E,et al.Relevance of serum levels of the endoplasmic reticulum stress protein GRP78(glucose-regulated protein 78 kDa) as biomarker in pulmonary diseases[J].Cell Stress Chaperones,2023;28(3):333-41.
25 Zhu ZW,Pu J,Li YN,et al.RBM25 regulates hypoxic cardiomyocyte apoptosis through CHOP-associated endoplasmic reticulum stress[J].Cell Stress Chaperones,2023;28(6):861-76.
26 焦凤娟.CDK5磷酸化XBP1s调控IRE1α/XBP1通路在帕金森病发病中的机制研究[D].武汉：华中科技大学，2018.
基本信息:
中图分类号:R742.5
引用信息:
[1]马田清,张三妮,韩淑辉,等.普拉克索对帕金森病小鼠多巴胺能神经元变性死亡及IRE1α/XBP-1通路的影响[J].中国老年学杂志,2026,46(15):2783-2789.
基金信息:
2019年度河南省医学科技攻关计划联合共建项目(LHGJ20190989)
2026-08-10
2026-08-10