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miR-124-5p通过靶向抑制STAT1促进帕金森大鼠小胶质细胞向M2型极化减轻脑损伤 被引量:2

miR-124-5p promotes M2-type polarization of microglia in Parkinson’s disease rats and alleviates brain injury by targeting STAT1
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摘要 目的探究miR-124-5p对帕金森大鼠脑黑质区小胶质细胞极化的作用及机制。方法Wistar雄性大鼠随机分为假手术组(Sham组)、帕金森组(PD组)和agomiR-124-5p组(agomiR组),每组10只。阿朴吗啡转诱导实验和异常不自主评分评价大鼠神经行为学;免疫荧光检测大鼠脑黑质TH阳性多巴胺神经元数量及M1型和M2型小胶质细胞数量;ELISA检测大鼠脑黑质炎症因子水平;生物信息学数据库预测与miR-124-5p结合的靶基因,双荧光素酶报告基因实验验证;qRT-PCR和Western blot检测大鼠黑质区STAT1表达。结果miR-124-5p改善帕金森大鼠神经行为学,增加大鼠脑黑质区神经元数量,降低M1型小胶质细胞分泌的炎症因子水平,增加M2型小胶质细胞分泌的炎症因子水平,驱动M2型小胶质细胞极化,miR-124-5p靶向结合STAT1,并降低帕金森大鼠脑黑质区STAT1表达。结论miR-124-5p通过靶向抑制STAT1表达,驱动帕金森大鼠小胶质细胞向M2型极化,改善脑损伤。 Objective To explore the effect and mechanism of miR-124-5p on microglia polarization in the substantia nigra of Parkinson’s disease rats.Methods Wistar male rats were randomly divided into sham group(Sham group),Parkinson’s disease group(PD group)and agomiR-124-5p group(agomiR group)with 10 rats in each group.The neurobehavior of rats was evaluated by the apogaline-induced transformation experiment and the abnormal involuntary score(AIM).The number of TH positive dopamine neurons and the number of M1-type and M2-type microglia in the substantia nigra were detected by immunofluorescence.The levels of inflammatory factors in the substantia nigra were detected by ELISA.The target genes combined with miR-124-5p were predicted by bioinformatics database and verified by dual luciferase reporter gene experiment.The expression of STAT1 in the substantia nigra was detected by qRT-PCR and Western blot.Results miR-124-5p improved the neurobehavior of Parkinson’s disease rats,increased the number of neurons in the substantia nigra,decreased the level of inflammatory factors secreted by M1-type microglia,increased the level of inflammatory factors secreted by M2-type microglia,and drove the polarization of M2-type microglia.miR-124-5p targeted to STAT1,and down-regulated the expression of STAT1 in the substantia nigra of Parkinson’s disease rats.Conclusion miR-124-5p drives M2-type polarization of microglia in Parkinson’s disease rats and improves brain damage by targeting STAT1.
作者 任占秀 张贺敏 付钟果 何秋 REN Zhan-xiu;ZHANG He-min;FU Zhong-guo;HE Qiu(Department of Neurology,Liaoning Provincial People's Hospital,Shenyang 110016,China)
出处 《解剖科学进展》 CAS 2022年第4期405-408,412,共5页 Progress of Anatomical Sciences
基金 辽宁省自然科学基金(2018011490-301)
关键词 miR-124-5p 帕金森病 STAT1 小胶质细胞极化 脑损伤 miR-124-5p Parkinson’s disease STAT1 microglia polarization brain damage
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  • 1McGeer PL, Itagaki S, McGeer EG. Expression of the histocompatibilityglycoprotein HLA-DR in neurological disease[J]. Acta Neuropathol, 1988, 76(6): 550-557.
  • 2Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson's disease: potential environmental triggers, pathways, and targets for early therapeutic intervention[J]. Exp Neurol, 2007, 208(1): 1-25.
  • 3D'Amours D, Desnoyers S, D'Silva I, et al. Poly(ADPribosyl)ation reactios in the regulation of nuclear functions[J]. Biochem, 1999, 342 (Pt 2): 249-286.
  • 4Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates, 2nd edn. Academic Press, San Diego, 2005.
  • 5Kim WG, Mohney RP, Wilson B, et al. Regional difference in susceptibility to lipopolysacchride-induced neurotoxicity in the rat brain: role of microglia[J]. Neurosci, 2000, 20:6309-6316.
  • 6Outeiro TF, Grammatopoulos TN, Altmann S, et al. Pharmacological inhibition of PARP- 1 reduces alpha-synuclein-and MPP+-induced cytotoxicity in Parkinson's disease in vitro models[J]. Biochem Biophys Res Commun, 2007, 357(3): 596-602.
  • 7Yokoyama H, Kuroiwa H, Tsukada T, et al. Poly(ADP-ribose) polymerse inhibitor can attenuate the neuronal death after 1- methyl-4-phenyl- 1,2,3,6- neurotoxclty in mice[J]. Neurosci Res,2010, 88(7): 1522-1536.
  • 8Moroni F. Poly(ADP-rihose)polymerase I(PARP-1) and postischemic rain damage[J]. Curr Opin Pharmacol, 2008, 8: 96-103.
  • 9Mota RA, S6nchez-Bueno F, Saenz L, et al. Inhibition of poly(ADP- ri-bose) polymerase attenuates the severity of acute pancreatitis and associated lung injury[J]. Lab Investn, 2005, 85: 1250-1262.
  • 10Scott GS, Kean RB, Mikheeva T, et al. The therapeutic effects of PJ34[N-(6-oxo-5, 6-dihydrophenanthridin-2-yl)-N, N- dimethylacetamide.HC1], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation[J]. Pharmacol Exp Ther, 2004, 310: 1053-1061.

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