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2ME2对脊髓损伤大鼠运动功能及Tau蛋白磷酸化的影响 被引量:5

Effect of 2-methoxyestradiol on phosphorylation of Tau protein and motor function of rats after spinal cord injury
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摘要 目的探讨2-甲氧基雌二醇(2ME2)对脊髓损伤大鼠运动功能及Tau蛋白磷酸化的影响。方法成年雄性SD大鼠72只按随机数字表法分为假手术组、脊髓损伤组和2ME2治疗组,每组24只。后2组大鼠采用改良的Allen’s法制作脊髓损伤大鼠模型。造模后1d 2ME2治疗组大鼠腹腔注射2ME2(24mg/kg),连续7d。脊髓损伤组大鼠注射等剂量生理盐水,假手术组不予干预。造模后1、3、7、14、21、28d应用BBB评分法对各组大鼠的后肢功能进行评分。造模后7d应用免疫荧光染色和Western blotting检测损伤脊髓磷酸化Tau蛋白(p-Tau)的表达。结果脊髓损伤组和2ME2治疗组大鼠脊髓损伤后1-28d随着时间的延长BBB评分升高,差异有统计学意义(P〈0.05)。损伤后7、14、21、28d2ME2治疗组大鼠BBB评分明显高于脊髓损伤组.差异有统计学意义(P〈0.05);与假手术组比较,脊髓损伤组和2ME2治疗组大鼠脊髓p-Tau阳性细胞数、蛋白表达均增加,且2ME2治疗组p-Tau阳性细胞数、蛋白表达(19.05±1.34、0.283±0.0941明显少于脊髓损伤组(10.36±1.28、0.607±0.105),差异均有统计学意义(P〈0.05)。结论2ME2可改善脊髓损伤大鼠的运动功能,具有一定的神经保护作用,其可能通过降低Tau蛋白磷酸化水平来实现。 Objective To investigate the effect of 2-methoxyestradiol (2ME2) on phosphorylation of Tau protein (p-Tau) and mortor function of rats after spinal cord injury (SCI). Methods A total of 72 adult male Sprague-Dawley rats were randomly divided into 3 groups: sham-operated group (n=24), SCI group (n=24) and SCI+2ME2 treated group (n=24); models of SCI were created by modified Alien's method; one d after SCI, rats in the SCI+2ME2 treated group were given intraperitoneal injection of 2ME2 (24 mg/kg) for seven d, and rats in the SCI group were given the same volume of normal saline. Basso, Beatti, Bresnahan (BBB) scale was performed to evaluate the hindlimb function one, three, seven, 14, 21 and 28 d after SCI; the expression changes of p-Tau (Ser 262) seven d after SCI were observed by immunofluorescence and Western blotting. Results BBB scale scores in the SCI group and SCI+2ME2 group were significantly increased following the prolonging of injury times (I-28 d of injury, P〈0.05); on the 7^th, 14^th, 21^st and 284 d of injury, the scores in the SCI+2ME2 group were significantly higher than those in the SCI group (P〈0.05). The p-Tau positive cells in the spinal cord and the p-Tau (Ser 262) expression in the SCI group and SCI+2ME2 group were significantly increased as compared with those in the sham-operated group (P〈0.05), and those in the SCI+2ME2 group (19.05±1.34 and 0.283±0.094) were obviously lower as compared with those in the SCI group (10.36±1,28 and 0.607±0.105, P〈0.05), Conclusion 2ME2 offers protection in rats with SCI by reducing the level of tau phosphorylation.
出处 《中华神经医学杂志》 CAS CSCD 北大核心 2014年第11期1127-1130,共4页 Chinese Journal of Neuromedicine
基金 国家临床重点建设专科资助项目 广东省神经外科临床中心资助项目
关键词 脊髓损伤 2.甲氧基雌二醇 TAU蛋白 磷酸化 Spinal cord injury 2-methoxyestradiol Tau protein Phosphorylation
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参考文献9

  • 1Mooberry SL. New insights into 2-methoxyestradiol, a promising antiangiogenic and antitumor agent[J]. Curr Opin Oncol, 2003, 15 (6): 425-430.
  • 2Mabjeesh N J, Escuin D, LaVallee TM, et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF[J]. Cancer Cell, 2003, 3(4): 363-375.
  • 3Basso DM, Beattie MS, Bresnahan JC. A sensitive and reli-ablelocomotor rating scale for open field testing in rats [J]. Neurotrauma, 1995, 12(1): 1-21.
  • 4Iqbal K, Gong CX, Liu F. Microtubule-associated protein tau as a therapeutic target in Alzheimer's disease [J]. Expert Opin Ther Targets, 2014, 18(3): 307-318.
  • 5Kopke E, Tung YC, Shaikh S, et al. Micrombule-associated protein tau. Abnormal phosphorylation of a non-paired helical filmqaent pool in Alzheimer disease [J]. J Biol Chem, 1993, 268 (32): 24374-24384.
  • 6Hung KS, Hwang SL, Liang CL, et al. Calpain inhibitor inhibits p35-p25-Cdk5 activation, decreases tan hyperphosphorylation, and improves neurological function after spinal cord hemisection in rats [J]. Neuropathol Exp Neurol, 2005, 64(1): 15-26.
  • 7Schaible EV, Windschugl J, Bobkiewicz W, et al. 2-Methoxyestradiol confers neuroprotection and inhibits a maladaptive HIF-1α response after traumatic brain injury in mice [J]. J Neurochem, 2014, 129(6): 940-954.
  • 8彭静华,张鸿日,黄丽娜,程小兵,崔涛,李云.2ME2对全脑缺血大鼠模型HIF—1α及凋亡相关基因的作用[J].中华神经医学杂志,2009,8(9):884-888. 被引量:5
  • 9Wang YF, Fan ZK, Cao Y, et al. 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury[J]. Brain Res, 2011, 1370(1): 220-226.

二级参考文献11

  • 1彭静华,李云,袁晓东,张鸿日,刘惠萍,赵东,汪运山.2ME2对全脑缺血大鼠HIF-1α的影响[J].山东医药,2007,47(1):9-10. 被引量:5
  • 2Kietzmann T, Knabe W, Schmidt-Kastner R. Hypoxia and hypoxia-inducible factor modulated gene expression in brain: involvement in neuroprotection and cell death [J]. Eur Arch Psychiatry Clin Neurosci, 2001, 251 (4): 170-178.
  • 3Greijer AE, van der Wall E. The role of hypoxia inducible factor 1 (H1F-1) in hypoxia induced apoptosis[J]. J Clin Pathol, 2004, 57 (10): 1009-1014.
  • 4Palsineli WA, Brieley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat[J]. Stroke, 1979, 10(3): 267-272.
  • 5Piret JP, Mottet D, Raes M, et al. Is HIF-1α a pro- or an anti-apoptotic protein? [J]. Biochem Pharmacol, 2002, 64(3): 889-892.
  • 6Chen W, Ostrowski RP, Obenaus A, et al. Prodeath or prosurvival: two facets ofhypoxia inducible factor-1 in perinatal brain injury[J]. Exp Neurol, 2009, 216(1): 7-15.
  • 7Helton R, Cui J, Scheel JR,et al. Brain-specific knock-out of hypoxia-inducible factor-1 reduces rather than increases hypoxic- ischemic damage [J]. J Neurosci, 2005, 25 (16): 4099-4107.
  • 8Dahut WL, Lakhani N J, Gullev JL, et al. Phase I clinical Trial of Oral 2-Methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors[J]. Cancer Biol Ther, 2006, 5(1): 22-27.
  • 9Li Y, Zhou C, Calvert JW, et al. Multiple effects of hyperbaric oxygen on the expression of HIF-1α and apoptotie genes in a global ischemia hypotension rat model [J]. Exp Neurol, 2005, 191 (1): 198-210.
  • 10Shoshani T, Faerman A, Mett I, et al. Identification of a novel hypoxia-inducible factor 1-responsive gene, RTPS01, involved in apoptosis[J]. Mol Cell Biol, 2002, 22(7): 2283-2293.

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  • 1Popiolek-Barczyk K, Kolosowska N, Piotrowska A, et al. Parthenolide relieves pain and promotes M2 Microglia/Macrophagepolarization in rat model ofneuropathy [J]. Neural Plast, 2015, 2015: 676473.
  • 2Tsuda M. Mechanisms underlying the pathogenesis of neuropathic pain revealing by the role of glial ceils [J]. Nihon Shinkei Seishin Yakurigaku Zasshi, 2015, 35(1): 1-4.
  • 3Clark AK, Gruber-Schoffnegger D, Drdla-Schutting R, et al. selective activation ofmicroglia facilitates synaptic strength [J]. J Neurosci, 2015, 35(11): 4552-4570.
  • 4Berliocchi L, Maiart M, Varano G P, et al. Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain [J]. Molecular pain, 2015, 11(1): 3.
  • 5Yin Q, Fan Q, Zhao Y, et al. Spinal NF-kappaB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model [J]. PloS one, 2015, 10(1): e0115120.
  • 6Choi YS, Jun IG, Kim SH, et al. Ilntrathecal lamotrigine attenuates mechanical allodynia and suppresses microglial and astrocytic activation in a rat model of spinal nerve ligation [J]. Yonsei Med J, 2013, 54(2): 321-329.
  • 7Dag E, Dag ZO, Baydas G, et al. Effects of lamotrigine and topiramate on brain maturation and cognitive functions in offspring of pregnant rats-preliminary study[J]. Adv Clin Exp Med, 2014, 23 (5): 691.
  • 8Floriddia EM, Rathore KI, Tedeschi A, et al. p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury[J]. J Neurosei, 2012, 32(40): 13956-13970.
  • 9Zhang MY, Zheng CY, Zou MM, et al. Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PSI transgenic mice[J]. Neurobiol Aging, 2014, 35(12): 2713-2725.
  • 10Nunes AF, Amaral JD, Lo AC, et al. TUDCA, a bile acid, attenuates amyloid precursor protein processing and amyloid-13 deposition in APP/PS1 mice [J]. Mol Neurobiol, 2012, 45 (3): 440-454.

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