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帕潘立酮对地佐环平损伤脑皮层神经元的保护作用及其机制 被引量:1

Protective effects and mechanisms of paliperidone on cortical neurons injured by dizocilpine
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摘要 目的探讨帕潘立酮对地佐环平损伤大鼠脑皮层神经元的保护作用及机制。方法取孕15 d胎鼠脑皮层神经元体外培养,应用地佐环平损伤神经元,然后加入不同浓度的帕潘立酮。采用MTT技术检测脑皮层神经元的生长活性,采用酶标仪检测乳酸脱氢酶(LDH)的活性及激光共聚焦技术检测神经元细胞内Ca2+浓度观察神经元凋亡情况,通过神经元突起数目及长度检测神经元生长情况,应用实时定量PCR技术检测Akt1、GSK3β的表达变化。结果与正常对照组相比,地佐环平损伤组神经元活性明显下降,LDH释放增加,细胞内游离钙离子浓度升高(P均<0.01),神经元突起总长度下降,神经突起数目呈现不同程度的减少(P<0.01),RT-PCR结果显示,Akt1及GSK3β表达下降(P<0.01);加入不同浓度的帕潘立酮能明显对抗地佐环平对神经元的损伤,MTT结果显示神经元活性升高(P<0.01),LDH活性明显降低(P<0.001),细胞内游离Ca2+浓度显著下降(P<0.01),神经突起数目和长度增加(P<0.01),Akt1及GSK3β表达上升(P<0.01)。结论帕潘立酮对地佐环平损伤脑皮层神经元具有明显保护作用,可抑制细胞凋亡,并通过Akt1-GSK3β通路促进神经突起的生长。 Objective To investigate protective effects of paliperidone on cortical neurons injured by dizocilpine and as- sociated mechanisms. Methods Cortical neurons were dissociated from embryonic rats at E15 and cultured in DMEM/ F12 medium supplemented with 10% fetal bovine serum. After cortical neurons were injured by dizocilpine, paliperi- done at different concentrations was added to detect their protection effects. MTT assay was adopted to detect cell viabil- ity. Lactate dehydrogenase (LDH) activity and intracellular Ca2 + concentration were measured with LDH cytotoxic as- say kit and laser scanning microscope respectively. Total length and number of neurites were calculated with Image Pro- Plus software, mRNA expressions of Aktl and GSK3β which associated with neurogenesis and neurodevelopment were detected by real-time PCR. Results In contrast with control group, cortical neurons in dizocilpine group exhibited ap- parently reduced viability, increased concentration of intracellular calcium and LDH release ( P 〈 0.01 ), declined num- ber and total length of neurites ( P 〈 0.01 ) and decreased expressions of Aktl and GSK3βat mRNA level detected by RT- PCR assay ( P 〈 0.01 ). Compared to dizocilpine group, viability of cultured cortical neurons was increased( P 〈 0.01 ) and LDH activity was declined due to the addition of paliperidone ( P 〈 0.001 ). Intracellular Ca2 * concentration in pali- peridone group was weaker than that in dizocilpine group ( P 〈 0.01 ). The length and number of neurites in paliperi- done group were greater than those in dizocilpine group ( P 〈 0.01 ). Real-time PCR also showed that the expressions of Aktl and GSK3β were higher in paliperidone group than those in dizocilpine group( P 〈 0.01 ). Conclusion Paliperi- done can effectively protect cortical neurons from dizocilpine injury, inhibit neuron apoptosis and promote neurogenesis via Aktl-GSK3β signaling pathway.
出处 《山东大学学报(医学版)》 CAS 北大核心 2012年第10期16-22,共7页 Journal of Shandong University:Health Sciences
基金 国家自然科学基金(81071081) 山东省自然科学基金(ZR2010HM051) 山东省科技发展计划(2011GSF11810)
关键词 脑皮层神经元 帕潘立酮 地佐环平 保护作用 Cortical neuron Paliperidone Dizocilpine Protection
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参考文献23

  • 1Tiedtke P I, Bischoff C, Schmidt W J. MK-801-induced stereotypy and its antagonism by neuroleptic drugs [ J ]. Neural Transm Gen Sect, 1990, 81 (3) :173-182.
  • 2吴金华,邹洪,于军,周雪东,谢青莲,金玫蕾.用不同实验小鼠品系建立精神分裂症的动物模型[J].生理学报,2003,55(4):381-387. 被引量:28
  • 3Rothman S. Noncompetitive N-methyl-D-aspartate antag- onists affect multiple ionic currents[J].Pharmacol Exp Ther, 1988, 246( 1 ) : 137-142.
  • 4Vergun O, Sobolevsky A I, Yelshansky M V, et al. Ex- ploration of the role of reactive oxygen species in gluta- mate neurotoxicity in rat hippocampal neurons in culture [ J]. Physiol, 2001, 531 ( 1 ) : 147-163.
  • 5Ahlgren H, Henjum K, Ottersen O P, et al. Validation of organotypical hippocampal slice cultures as an ex vivo model of brain ischemia- different roles of NMDA recep- tors in cell death signaling after exposure to NMDA or ox- ygen and glucose deprivation[ J]. Cell Tissue Res, 2011, 345 (3) ,329-341.
  • 6Leung J C, Ragland N, Marphis T, et al. NMDA ago- nists and antagonists induce renal culture cell toxicity [J].Med Chem. 2008. 4(6) ,565-571.
  • 7Ono T, Hashimoto E, Ukai W, et al. The role of neuralstem cells for in vitro models of schizophrenia: neuropro- tection via Akt/ERK signal regulation [ J ]. Schizophr Res, 2010, 122(1-3) :239-247.
  • 8Emamian E S, Hall D, Bimbaum M J, et al. Convergent evidence for impaired KT1-GSK3beta signaling in schizo- phrenia[J].Nat Genet,2004, 36(2) :131-137.
  • 9Desbonnet L, Waddington J L, Tuathaigh C M, et al. Mice mutant for genes associated with schizophrenia: common phenotype or distinct endophenotypes[J]. Behav Brain Res, 2009, 204(2):258-273.
  • 10刘振花,郑云哨,张天亮,安璐璇.帕利哌酮缓释片对急性期精神分裂症患者社会功能的影响[J].山东大学学报(医学版),2011,49(8):100-103. 被引量:4

二级参考文献24

  • 1牛雅娟,黄文升,郝学儒,杨甫德,吉中孚.氯氮平和利培酮治疗精神分裂症患者比较研究[J].上海精神医学,2003,15(5):276-278. 被引量:10
  • 2Jones P B, Barnes T R, Davies L. Randomized controlled trial of the effect on quality of life of second-vs ftrst-generation antipsychotic drugs in schizophrenia: cost utility of the latest antipsychofic drugs in schizophrenia study ( CUt-LASS 1 ) [ J ]. Arch Gen Psychiatry, 2006, 63 (10) : 1079-1087.
  • 3Janicak P G, Winans E A. Paliperidone E R: a review of the clinical trial data[ J]. Neuropsychiatr Dis Treat, 2007, 3 (6) : 869-897.
  • 4Meltzer H Y, Bobo W V, Nuamah I F, et al. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6 week, placebo-controlled studies [ J ]. J Clin Psychiatry, 2008, 69(5):817-829.
  • 5Morosini P L, Magtiano L, Brambilla L, et al. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale( SOFAS ) to assess routine social functioning [ J ]. Acta Psvchiatr Scand. 2000. 101 (4):323-329.
  • 6Fowler J A, Bettinger T L, Argo T R. Paliperidone extended-release tablets for the acute and maintenance treatment of schizophrenia [ J ]. Clin Ther, 2008, 30 ( 2 ) : 231-248.
  • 7Kramer M, Simpson G, Maciulis V, et al. Paliperidone ex-tended release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study[ J]. J Clin Psyehopharmacol, 2007, 27(1) :6-14,.
  • 8Patrick D L, Burns T, Morosini P, et al. Measuring social functioning with the personal and social performance scale in patients with acute symptoms of schizophrenia: interpretation of results of a pooled analysis of three Phase III trials of paliperidone extended-release tablets [J]. Clin Ther, 2010, 32(2) :275-292.
  • 9Canuso C M, Youssef E A, Bossie C A, et al. Paliperidone extended-release tablets in schizophrenia patients previously treated with risperidone [ J ]. Int Clin Psychopharmacol, 2008, 23(4):209-215.
  • 10Warner R, Girolamo D. Schizophrenia. Geneva: World Health Organization, 1995.

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