耐药性癫痫患者外周血N-WASP基因表达的研究
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摘要
目的观察神经元威斯科特-奥德里奇综合征蛋白(Neural Wiskott-Aldrich syndrome protein,N-WASP)基因在耐药性癫痫(drug resistant epilepsy,DRE)患者外周血中的表达变化,分析其作为外周血生物学指标预测DRE的临床价值。方法抽取32例DRE患者(耐药组)、40例抗癫痫药物控制良好者(良好组)及32例健康体检者(正常组)的外周血。采用RT-PCR检测3组人群外周血N-WASP基因相对表达量,分析比较不同用药方式、不同病程及用药前不同癫痫发作频率N-WASP基因相对表达量差异。结果耐药组外周血N-WASP基因相对表达量显著高于良好组(P<0.01),良好组显著高于正常组(P<0.01)。2种药物联合治疗无效组N-WASP基因相对表达量显著高于2种药物联合治疗有效组(P=0.035),2种药物联合治疗有效组高于单药治疗有效组,差异无统计学意义(P=0.789)。耐药组和良好组中病程≥5年组N-WASP基因相对表达量均显著高于病程<5年组(P<0.001)。耐药组和良好组中用药前癫痫发作频率≥4次/月亚组的N-WASP基因相对表达量均显著高于发作频率<4次/月亚组(P=0.016,P<0.001)。结论N-WASP基因表达量在DRE患者外周血中明显升高并且与药物疗效差、病程长和发作频率高密切相关,提示其可能参与了DRE的发生和发展,或可以作为预测DRE发生的外周血生物学指标之一。
Objective To analyze the clinical value of Neural Wiskott-Aldrich syndrome protein(NWASP)mRNA as a biomarker for forecasting drug resistant epilepsy(DRE)by observing the relative expression of peripheral blood N-WASP mRNA in patients with DRE. Methods Blood samples were drawn from 32 patients with DRE(DRE group),40 patients well controlled with anti-epileptic drugs(AEDs)(AEDs well controlled group)and 32 healthy individuals(normal group).The relative expression of peripheral blood NWASP mRNA was measured by RT-PCR for the three groups.Analysis and comparison of N-WASP mRNA relative expression were performed among different drug regimens,different course of disease and different seizure frequency before drug administration. Results The relative expression of N-WASP mRNA was significantly higher in the DRE group than that in the AEDs well controlled group(P <0.01).The relative expression of N-WASP mRNA was significantly higher in the AEDs well controlled group than that in the normal group(P <0.01).The relative expression of N-WASP mRNA was significantly higher in the ineffective group with two drugs combined therapy than that in the effective group with two drugs combined therapy(P =0.035).The relative expression of N-WASP mRNA was higher in the effective group with two drugs combined therapy than that in the effective group with single drug therapy,there was no statistical difference(P =0.789).The relative expression of N-WASP mRNA was significantly higher in the≥5-year disease course subgroup than that in the<5-year disease course subgroup in the DRE group and AEDs well controlled group(P<0.001).The relative expression of N-WASP mRNA was significantly higher in patients having more than 4 seizures times per month subgroup before treatment than those having less than 4 seizures times per month subgroup group in the DRE and AEDs well controlled groups(P =0.016,P <0.001). Conclusion The expression level of peripheral blood N-WASP mRNA is significantly increased in DRE patients and is closely related to poor drug efficacy,long disease course and high frequency of seizures,suggesting that it may be involved in the occurrence and development of DRE,and it may be one of peripheral blood biomarkers for predicting DRE occurrence.
Objective To analyze the clinical value of Neural Wiskott-Aldrich syndrome protein(NWASP)mRNA as a biomarker for forecasting drug resistant epilepsy(DRE)by observing the relative expression of peripheral blood N-WASP mRNA in patients with DRE. Methods Blood samples were drawn from 32 patients with DRE(DRE group),40 patients well controlled with anti-epileptic drugs(AEDs)(AEDs well controlled group)and 32 healthy individuals(normal group).The relative expression of peripheral blood NWASP mRNA was measured by RT-PCR for the three groups.Analysis and comparison of N-WASP mRNA relative expression were performed among different drug regimens,different course of disease and different seizure frequency before drug administration. Results The relative expression of N-WASP mRNA was significantly higher in the DRE group than that in the AEDs well controlled group(P <0.01).The relative expression of N-WASP mRNA was significantly higher in the AEDs well controlled group than that in the normal group(P <0.01).The relative expression of N-WASP mRNA was significantly higher in the ineffective group with two drugs combined therapy than that in the effective group with two drugs combined therapy(P =0.035).The relative expression of N-WASP mRNA was higher in the effective group with two drugs combined therapy than that in the effective group with single drug therapy,there was no statistical difference(P =0.789).The relative expression of N-WASP mRNA was significantly higher in the≥5-year disease course subgroup than that in the<5-year disease course subgroup in the DRE group and AEDs well controlled group(P<0.001).The relative expression of N-WASP mRNA was significantly higher in patients having more than 4 seizures times per month subgroup before treatment than those having less than 4 seizures times per month subgroup group in the DRE and AEDs well controlled groups(P =0.016,P <0.001). Conclusion The expression level of peripheral blood N-WASP mRNA is significantly increased in DRE patients and is closely related to poor drug efficacy,long disease course and high frequency of seizures,suggesting that it may be involved in the occurrence and development of DRE,and it may be one of peripheral blood biomarkers for predicting DRE occurrence.
引文
[1]Kwan P,Arzimanoglou A,Berg A T,et al.Definition of drug resistant epilepsy:consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies[J].Epilepsia,2010,51(6):1069-77.
[2]Engel JJr,International League Against Epilepsy(ILAE).A proposed diagnostic scheme for people with epileptic seizures and with epilepsy:report of the ILAE Task Force on Classification and Terminology[J].Epilepsia,2001,42(6):796-803.
[3]Miki H,Miura K,Takenawa T.N-WASP,a novel actindepolymerizing protein,regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases[J].EMBO J,1996,15(19):5326-5335.
[4]Luan Q,Zelter A,MacCoss MJ,et al.Identification of Wiskott-Aldrich syndrome protein(WASP)binding sites on the branched actin filament nucleator Arp2/3complex[J].Proc Natl Acad Sci USA,2018,115(7):E1409-E1418.
[5]Novak N,Bar V,Sabanay H,et al.N-WASP is required for membrane wrapping and myelination by Schwann cells[J].J Cell Biol,2011,192(2):243-50.
[6]Xiao F,Wang X,Li J,et al.Overexpression of N-WASP in the brain of human epilepsy[J].Brain Res,2008,1233:168-75.
[7]沈秀莲,逯宜超,甲芝莲,等.N-WASP通过polyPro和VCA结构域调控大脑皮层神经元迁移[J].遗传,2018,40(5):390-401.
[8]Hebbrecht T,Van Audenhove I,Zwaenepoel O,et al.VCA nanobodies target N-WASp to reduce invadopodium formation and functioning[J].PLoS One,2017,12(9):e0185076.
[9]Kitamura Y,Tsuchiya D,Takata K,et al.Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in Alzheimer’s disease[J].Neurosci Lett,2003,346(3):149-152.
[10]李乐超,张燕芳.耐药性部分性发作癫痫抗癫痫药物治疗观察及影响因素分析[J].山东医药,2013,53(23):24-26.
[11]胡春霞,郑维红,刘肇绩,等.耐药性癫痫的相关危险因素分析[J].医学综述,2015,21(14):2642-2644.
[2]Engel JJr,International League Against Epilepsy(ILAE).A proposed diagnostic scheme for people with epileptic seizures and with epilepsy:report of the ILAE Task Force on Classification and Terminology[J].Epilepsia,2001,42(6):796-803.
[3]Miki H,Miura K,Takenawa T.N-WASP,a novel actindepolymerizing protein,regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases[J].EMBO J,1996,15(19):5326-5335.
[4]Luan Q,Zelter A,MacCoss MJ,et al.Identification of Wiskott-Aldrich syndrome protein(WASP)binding sites on the branched actin filament nucleator Arp2/3complex[J].Proc Natl Acad Sci USA,2018,115(7):E1409-E1418.
[5]Novak N,Bar V,Sabanay H,et al.N-WASP is required for membrane wrapping and myelination by Schwann cells[J].J Cell Biol,2011,192(2):243-50.
[6]Xiao F,Wang X,Li J,et al.Overexpression of N-WASP in the brain of human epilepsy[J].Brain Res,2008,1233:168-75.
[7]沈秀莲,逯宜超,甲芝莲,等.N-WASP通过polyPro和VCA结构域调控大脑皮层神经元迁移[J].遗传,2018,40(5):390-401.
[8]Hebbrecht T,Van Audenhove I,Zwaenepoel O,et al.VCA nanobodies target N-WASp to reduce invadopodium formation and functioning[J].PLoS One,2017,12(9):e0185076.
[9]Kitamura Y,Tsuchiya D,Takata K,et al.Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in Alzheimer’s disease[J].Neurosci Lett,2003,346(3):149-152.
[10]李乐超,张燕芳.耐药性部分性发作癫痫抗癫痫药物治疗观察及影响因素分析[J].山东医药,2013,53(23):24-26.
[11]胡春霞,郑维红,刘肇绩,等.耐药性癫痫的相关危险因素分析[J].医学综述,2015,21(14):2642-2644.