重组人促红细胞生成素对创伤性脑损伤小鼠学习记忆能力的影响
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摘要
目的研究重组人促红细胞生成素(rhEPO)对创伤性脑损伤(TBI)小鼠海马CA1区突触素蛋白(SYP)表达和神经元分布的影响,以及皮质损伤周边区神经丝蛋白(NF-H)的表达及对学习记忆能力的影响。方法将30只小鼠随机分为假手术组(sham组)、模型组[控制性皮层冲击损伤(CCI)组]和rhEPO治疗组(rhEPO组),每组10只。CCI组和rhEPO组采用CCI制作重型TBI模型。rhEPO组建模后立即按质量分数5 000U/(kg·d)腹腔注射rhEPO,连续给药7d。TBI后21d,新物体识别检测小鼠学习记忆力;免疫荧光测定小鼠海马CA1区SYP、神经元分布和皮质损伤周边区NF-H的表达;western blotting测定小鼠海马SYP和皮质损伤周边区NF-H的表达。结果 rhEPO组小鼠的新物体偏爱指数高于CCI组,差异有统计学意义(P<0.05)。免疫荧光提示rhEPO组较CCI组皮质损伤周边区NF-H破坏减少,海马CA1区SYP表达升高,神经元丢失减少,差异均有统计学意义(P<0.05)。Western blotting测得rhEPO组海马SYP及皮质损伤周边区NF-H表达均较CCI组高,差异均有统计学意义(P<0.05)。结论 rhEPO可以促进小鼠TBI后海马CA1区SYP表达,减少海马CA1区神经元丢失及皮质损伤周边区NF-H降解,改善小鼠TBI后学习记忆能力。
Objective To explore the effect of recombinant human erythropoietin(rhEPO)on expression of synaptophysin(SYP)and distribution of neurons in the hippocampal CA1 region of TBI mice,and the expression of neurofilament protein(NF-H)around injury cortex and the effect of learning and memory ability.Methods A total of 30 mice were randomly divided into sham operation group(sham group),model group[controlled cortical impact(CCI)group]and rhEPO treatment group(rhEPO group),10 in each group.A severe TBI models of mouse were made by CCI in CCI group and rhEPO group.After the impact,rhEPO group was intraperitoneally injected with rhEPO immediately at 5 000 U/(kg·d)for 7 d.The new object recognition test was performed at 21 dafter injury.The expression of SYP and distribution of neurons in the hippocampal CA1 region and the expression of NF-H around injured cortex were detected by immunofluorescence and western blotting.Results The new object preference index of rhEPO group was higher than that of CCI group,the difference was statistically significant(P<0.05).The immunofluorescence showed those rhEPO group compared with the CCI group,which the degradation of NF-H around injured area was decreased,the expression of SYP in hippocampal CA1 area was increased,and the loss of neurons was attenuated,the differences were statistically significant(P<0.05).The expression of SYP in the hippocampal and the expression of NF-H around injured area detected by western blotting show that rhEPO group were higher than CCI group,the differences were statistically significant(P<0.05).Conclusion After TBI,rhEPO can promote the expression of SYP in hippocampal CA1 area,reduce the loss of neuron in hippocampal CA1 area and the degradation of NF-H around injured area,and improve the learning and memory ability.
Objective To explore the effect of recombinant human erythropoietin(rhEPO)on expression of synaptophysin(SYP)and distribution of neurons in the hippocampal CA1 region of TBI mice,and the expression of neurofilament protein(NF-H)around injury cortex and the effect of learning and memory ability.Methods A total of 30 mice were randomly divided into sham operation group(sham group),model group[controlled cortical impact(CCI)group]and rhEPO treatment group(rhEPO group),10 in each group.A severe TBI models of mouse were made by CCI in CCI group and rhEPO group.After the impact,rhEPO group was intraperitoneally injected with rhEPO immediately at 5 000 U/(kg·d)for 7 d.The new object recognition test was performed at 21 dafter injury.The expression of SYP and distribution of neurons in the hippocampal CA1 region and the expression of NF-H around injured cortex were detected by immunofluorescence and western blotting.Results The new object preference index of rhEPO group was higher than that of CCI group,the difference was statistically significant(P<0.05).The immunofluorescence showed those rhEPO group compared with the CCI group,which the degradation of NF-H around injured area was decreased,the expression of SYP in hippocampal CA1 area was increased,and the loss of neurons was attenuated,the differences were statistically significant(P<0.05).The expression of SYP in the hippocampal and the expression of NF-H around injured area detected by western blotting show that rhEPO group were higher than CCI group,the differences were statistically significant(P<0.05).Conclusion After TBI,rhEPO can promote the expression of SYP in hippocampal CA1 area,reduce the loss of neuron in hippocampal CA1 area and the degradation of NF-H around injured area,and improve the learning and memory ability.
引文
[1] ARULSAMY A,CORRIGAN,COLLINS-PRAINO LE.Cognitive and neuropsychiatric impairments vary as a function of injury severity at 12 months post-experimental diffuse traumatic brain injury:implications for dementia development[J].Behav Brain Res,2019,365:66-76.
[2] KRUKOWSKI K,CHOU A,FENG X,et al.traumatic brain injury in aged mice induces chronic microglia activation,synapse loss,and complement-dependent memory deficits[J].Int J Mol Sci,2018,19(12):E3753.
[3] VALLAT-AZOUVI C,AZOUVI P,LE-BORNEC G,et al.Treatment of social cognition impairments in patients with traumatic brain injury:a critical review[J/OL].Brain Inj,2018-10-22[2018-12-10].https://www.ncbi.nlm.nih.gov/pubmed/?term=Treatment+of+social+cognition+impairments+in+patients+with+traumatic+brain+injury%3A+a+critical+review.
[4]高梦颖,何永昌,孙国柱,等.大鼠液压冲击脑损伤Nrf2、HO-1和NQO-1动态表达变化及意义[J].第三军医大学学报,2016,38(18):2023-2028.
[5]李娟,常子嵩,姚遥,等.黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响[J].南京中医药大学学报,2018,34(6):597-601.
[6] MIRZA FJ.The role of synapsins in neurological disorders[J].Neurosci Bull,2018,34(2):349-358.
[7] KOIKE K,TSUKADA S,TSUZUKI K,et al.Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing[J].J Neurosci,2000,20(6):2166-2174.
[8]INKSTER B,ZAI G,LEWIS G.GSK3β:aplausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?[J].Translat Psych,2018,8(1):216.
[9]于若谷,赵聪敏,王丽雁,等.丰富环境刺激对缺氧缺血性脑损伤大鼠脑神经丝蛋白表达的影响[J].第三军医大学学报,2006,28(20):2065-2067.
[10]MIRZA FJ,ZAHID S.The role of synapsins in neurological disorders[J].Neurosci Bull,2018,34(2):349-358.
[11]KOIKE K,TSUKADA S,TSUZUKI K,et al.Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing[J].J Neurosci,2000,20(6):2166-2174.
[2] KRUKOWSKI K,CHOU A,FENG X,et al.traumatic brain injury in aged mice induces chronic microglia activation,synapse loss,and complement-dependent memory deficits[J].Int J Mol Sci,2018,19(12):E3753.
[3] VALLAT-AZOUVI C,AZOUVI P,LE-BORNEC G,et al.Treatment of social cognition impairments in patients with traumatic brain injury:a critical review[J/OL].Brain Inj,2018-10-22[2018-12-10].https://www.ncbi.nlm.nih.gov/pubmed/?term=Treatment+of+social+cognition+impairments+in+patients+with+traumatic+brain+injury%3A+a+critical+review.
[4]高梦颖,何永昌,孙国柱,等.大鼠液压冲击脑损伤Nrf2、HO-1和NQO-1动态表达变化及意义[J].第三军医大学学报,2016,38(18):2023-2028.
[5]李娟,常子嵩,姚遥,等.黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响[J].南京中医药大学学报,2018,34(6):597-601.
[6] MIRZA FJ.The role of synapsins in neurological disorders[J].Neurosci Bull,2018,34(2):349-358.
[7] KOIKE K,TSUKADA S,TSUZUKI K,et al.Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing[J].J Neurosci,2000,20(6):2166-2174.
[8]INKSTER B,ZAI G,LEWIS G.GSK3β:aplausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?[J].Translat Psych,2018,8(1):216.
[9]于若谷,赵聪敏,王丽雁,等.丰富环境刺激对缺氧缺血性脑损伤大鼠脑神经丝蛋白表达的影响[J].第三军医大学学报,2006,28(20):2065-2067.
[10]MIRZA FJ,ZAHID S.The role of synapsins in neurological disorders[J].Neurosci Bull,2018,34(2):349-358.
[11]KOIKE K,TSUKADA S,TSUZUKI K,et al.Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing[J].J Neurosci,2000,20(6):2166-2174.