电针风池穴对脑缺血再灌注大鼠突触素、生长相关蛋白-43的影响
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摘要
目的观察电针风池穴对脑缺血再灌注大鼠突触素(synaptophysin, SYN)、生长相关蛋白-43(growth associated protein-43, GAP-43)表达变化的影响。方法将32只SD雄性大鼠随机分为正常组、假手术组、模型组、电针组,每组8只。模型组和电针组采用线栓法制作脑缺血再灌注模型。采用电针双侧风池穴对电针组大鼠进行治疗,每日1次,每次30 min,至动物处死。应用免疫组织化学法检测SYN和GAP-43的表达。结果模型组和电针组造模后2 h和造模后6 d Bederson评分与正常组和假手术组比较,差异均有统计学意义(P<0.05)。模型组和电针组造模后6 d海马和皮层SYN IOD值和GAP-43 IOD值与正常组和假手术组比较,差异均具有统计学意义(P<0.05)。电针组造模后6 d海马和皮层SYN IOD值和GAP-43 IOD值与模型组比较,差异均具有统计学意义(P<0.05)。结论电针风池穴可促进脑缺血再灌注模型大鼠的GAP-43和SYN的表达,表明电针可以促进轴突再生,对突触的可塑性具有正向改善作用。
Objective To study the effect of electroacupuncture at Fengchi(GB20) on the expressions of synaptophysin(SYN) and growth associated protein-43(GAP-43) in rats with ischemia/reperfusion(I/R) injury Method Thirty-two male Sprague-Dawley(SD) rats were randomized into normal, sham operation, model and electroacupuncture groups, with 8 rats in each group. The middle cerebral artery occlusion(MCAO) rat model was generated by thread embolization in the model and electroacupuncture groups. The electroacupuncture group received electroacupuncture at bilateral Fengchi(GB20), once a day, 30 min each time, until the rats were executed. The expressions of SYN and GAP-43 were examined by immunohistochemistry method. Result The Bederson scores2 hours and 6 days after modeling in the model and electroacupuncture groups were significantly different from those in the normal and sham operation groups(P<0.05). The integrated optical density(IOD) values of SYN and GAP-43 in hippocampus and cortex 6 days after modeling in the model and electroacupuncture groups were significantly different from those in the normal and sham operation groups(P<0.05). The IOD values of SYN and GAP-43 in hippocampus and cortex 6 days after modeling in the electroacupuncture group were significantly different from those in the model group(P<0.05). Conclusion Electroacupuncture at Fengchi(GB20) can promote the expressions of SYN and GAP-43 in rats with I/R injury, which suggests that electroacupuncture can promote axon regeneration and improve synaptic plasticity.
Objective To study the effect of electroacupuncture at Fengchi(GB20) on the expressions of synaptophysin(SYN) and growth associated protein-43(GAP-43) in rats with ischemia/reperfusion(I/R) injury Method Thirty-two male Sprague-Dawley(SD) rats were randomized into normal, sham operation, model and electroacupuncture groups, with 8 rats in each group. The middle cerebral artery occlusion(MCAO) rat model was generated by thread embolization in the model and electroacupuncture groups. The electroacupuncture group received electroacupuncture at bilateral Fengchi(GB20), once a day, 30 min each time, until the rats were executed. The expressions of SYN and GAP-43 were examined by immunohistochemistry method. Result The Bederson scores2 hours and 6 days after modeling in the model and electroacupuncture groups were significantly different from those in the normal and sham operation groups(P<0.05). The integrated optical density(IOD) values of SYN and GAP-43 in hippocampus and cortex 6 days after modeling in the model and electroacupuncture groups were significantly different from those in the normal and sham operation groups(P<0.05). The IOD values of SYN and GAP-43 in hippocampus and cortex 6 days after modeling in the electroacupuncture group were significantly different from those in the model group(P<0.05). Conclusion Electroacupuncture at Fengchi(GB20) can promote the expressions of SYN and GAP-43 in rats with I/R injury, which suggests that electroacupuncture can promote axon regeneration and improve synaptic plasticity.
引文
[1]孙海欣,王文志.中国60万人群脑血管病流行病学抽样调查报告[J].中国现代神经疾病杂志,2018,18(2):83-88.
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[6]Udvadia AJ,K?ster RW,Skene JH.GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration[J].Development,2001,128(7):1175-1182.
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[8]Bederson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke1986,17(3):472-476.
[9]詹剑,李小琼,郝仁方.金钗石斛多糖对局灶性脑缺血-再灌注大鼠的作用[J].中国脑血管病杂志,2017,14(1):25-31.
[10]徐鸣曙,葛林宝,徐佳,等.电针对脑缺血再灌注大鼠纹状体内单胺类递质更新率的影响[J].上海针灸杂志,2009,28(4):239-242.
[11]Hasan A,Nitsche MA,Rein B,et al.Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation[J].Behav Brain Res,2011,224(1):15-22.
[12]Maeda I,Tajima S,Ariizumi Y,et al.Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?[J].Pathol Int,2016,66(7):369-375.
[13]Yadav L,Babu MK,Das K,et al.Role of synaptophysin in the intraoperative assessment of quadrantic innervation of the proximal doughnut in Hirschsprung disease[J].Natl Med J India,2017,30(4):187-192.
[14]Griva M,Lagoudaki R,Touloumi O,et al.Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior,BDNF and synaptophysin levels in rat hippocampus:Effect of combined treatment with G-CSF[J].Brain Res,2017,1667:55-67.
[15]Xiao Z,Peng J,Wu L,et al.The effect of IL-1βon synaptophysin expression and electrophysiology of hippo campal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy[J].Neurol Res,2017,39(7):640-648.
[16]Chen YY,Zhang L,Shi DL,et al.Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus[J].Ann Clin Lab Sci2017,47(1):17-24.
[17]Matsukuma K,Olson KA,Gui D,et al.SynaptophysinKi67 double stain:a novel technique that improves interobserver agreement in the grading of welldifferentiated gastrointestinal neuroendocrine tumors[J].Mod Pathol,2017,30(4):620-629.
[18]Tudora?cu DR,Pirici D,Tartea EA,et al.Synaptophysin expression as prognostic factor for survival in colorectal carcinomas[J].Rom J Morphol Embryol,2017,58(4):1409-1415.
[19]朱旭红,张萍淑,程赞赞,等.突触可塑性相关蛋白及其与临床疾病的关系[J].华北理工大学学报(医学版),2017,19(3):237-241.
[20]Stroemer RP,Kent TA,Hulsebosch CE.Neocortical neural sprouting,synaptogenesis,and behavioral recovery after neocortical infarction in rats[J].Stroke,1995,26(11):2135-2144.
[21]Madinier A,Bertrand N,Mossiat C,et al.Microglial involvement in neuroplastic changes following focal brain ischemia in rats[J].PLoS One,2013,4(12):e8101.
[22]Yi W,Xu NG,Wang GB.Experimental study on effects of electro-acupuncture in improving synaptic plasticity in focal cerebral ischemia rats[J].Zhongguo Zhong Xi Yi Jie He Za Zhi,2006,26(8):710-714.
[23]Xia WG,Zheng CJ,Zhang X,et al.Effects of"nourishing liver and kidney"acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats[J].J Huazhong Univ Sci Technolog Med Sci,2017,37(2):271-278.
[24]陈鹏,张大雁,吴思苇,等.电针结合天麻素增加局灶性脑缺血大鼠额叶皮质生长相关蛋白-43以及突触素的免疫组化表达[J].医学理论与实践,2017,30(1):1-3.
[25]赵嘉培,黄丹霞,黄赛娥,等.电针“曲池”和“足三里”对脑缺血大鼠皮质突触素、脑源性神经营养因子表达的影响[J].中国动脉硬化杂志,2017,25(11):1099-1106.
[26]Coggins PJ,Zwiers H.B-50(GAP-43):biochemistry and functional neurochemistry of a neuron-specific phosphorprotein[J].J Neurochem,1991,56(4):1095-1106.
[27]Zhu X,Wang P,Liu H,et al.Changes and Significance of SYP and GAP-43 Expression in the Hippocampus of CIH Rats[J].Int J Med Sci,2019,16(3):394-402.
[28]Martins CW,de Melo Rodrigues LC,Nitsche MA,et al.AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression[J].Behav Brain Res,2019,362:208-212.
[29]Nemes AD,Ayasoufi K,Ying Z,et al.Growth Associated Protein 43(GAP-43)as a Novel Target for the Diagnosis,Treatment and Prevention of Epileptogenesis[J].Sci Rep,2017,7(1):17702.
[30]Han XF,Zhang Y,Xiong LL,et al.Erratum to:Lentiviral-Mediated Netrin-1 Overexpression Improves Motor and Sensory Functions in SCT Rats Associated with SYP and GAP-43 Expressions[J].Mol Neurobiol,2017,54(3):1698.
[31]Gorup D,Boha?ek I,Mili?evi?T,et al.Increased expression and colocalization of GAP43 and CASP3after brain ischemic lesion in mouse[J].Neurosci Lett,2015,597:176-182.
[32]石旺清,郑关毅,陈晓东,等.大鼠脑缺血/再灌注后bFGF和GAP-43的表达与神经再生[J].中国应用生理学杂志,2013,29(1):63-67.
[33]张鹏飞,徐成成,李文磊,等.电针对局灶性脑缺血大鼠10号染色体同源丢失性磷酸酶张力蛋白和神经生长相关蛋白-43表达的影响[J].中国康复理论与实践,2015,21(1):35-38.
[34]卿鹏,柴铁劬,丁红梅,等.双侧电针结合康复训练对局灶性脑缺血/再灌注损伤大鼠海马CA3区神经生长相关蛋白43及突触素表达的影响[J].针刺研究,2016,41(4):314-320.
[35]刘斐雯,俞坤强,彭洪卫,等.电针百会、神庭穴对局灶性脑缺血再灌注大鼠学习记忆能力及海马区GAP-43蛋白表达的影响[J].中国中医急症,2016,25(2):189-192,207.
[36]周元成,吴新贵,肖贻财.电针刺激“足三里”和“内关”对脑梗死大鼠GAP-43表达的影响[J].中国针灸,2011,31(1):55-59.
[37]张晨茜,储浩然,程红亮,等.针刺风池、风府穴对缺血性脑卒中患者血浆内皮素的影响[J].上海针灸杂志,2012,31(1):15-17.
[38]徐佳,徐鸣曙.电针对大鼠脑缺血-再灌注过程中体感诱发电位P1-N1、N1-P2峰峰值变化的影响[J].上海针灸杂志,2010,29(8):542-545.
[39]秦彦强,孙忠人,魏庆双,等.针刺风池穴预处理对脑梗死大鼠的缺血耐受现象研究[J].针灸临床杂志,2015,31(9):65-68.
[2]宋宛珊,郭威,张玉莲,等.突触可塑性相关物质基础研究进展[J].中国老年学杂志,2015,35(17):5039-5042.
[3]Gispen WH.Neuronal plasticity and function[J].Clin Neuropharmacol,1993,16(Suppl 1):S5-S11.
[4]郭敏,李刚.突触可塑性相关蛋白的研究进展[J].神经药理学报,2013,3(6):57-64.
[5]Coggins PJ,Zwiers H.B-50(GAP-43):biochemistry and functional neurochemistry of a neuron-specific phosphoprotein[J].J Neurochem,1991,56(4):1095-1106.
[6]Udvadia AJ,K?ster RW,Skene JH.GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration[J].Development,2001,128(7):1175-1182.
[7]Longa EZ,Weinstein PR,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[8]Bederson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke1986,17(3):472-476.
[9]詹剑,李小琼,郝仁方.金钗石斛多糖对局灶性脑缺血-再灌注大鼠的作用[J].中国脑血管病杂志,2017,14(1):25-31.
[10]徐鸣曙,葛林宝,徐佳,等.电针对脑缺血再灌注大鼠纹状体内单胺类递质更新率的影响[J].上海针灸杂志,2009,28(4):239-242.
[11]Hasan A,Nitsche MA,Rein B,et al.Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation[J].Behav Brain Res,2011,224(1):15-22.
[12]Maeda I,Tajima S,Ariizumi Y,et al.Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?[J].Pathol Int,2016,66(7):369-375.
[13]Yadav L,Babu MK,Das K,et al.Role of synaptophysin in the intraoperative assessment of quadrantic innervation of the proximal doughnut in Hirschsprung disease[J].Natl Med J India,2017,30(4):187-192.
[14]Griva M,Lagoudaki R,Touloumi O,et al.Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior,BDNF and synaptophysin levels in rat hippocampus:Effect of combined treatment with G-CSF[J].Brain Res,2017,1667:55-67.
[15]Xiao Z,Peng J,Wu L,et al.The effect of IL-1βon synaptophysin expression and electrophysiology of hippo campal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy[J].Neurol Res,2017,39(7):640-648.
[16]Chen YY,Zhang L,Shi DL,et al.Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus[J].Ann Clin Lab Sci2017,47(1):17-24.
[17]Matsukuma K,Olson KA,Gui D,et al.SynaptophysinKi67 double stain:a novel technique that improves interobserver agreement in the grading of welldifferentiated gastrointestinal neuroendocrine tumors[J].Mod Pathol,2017,30(4):620-629.
[18]Tudora?cu DR,Pirici D,Tartea EA,et al.Synaptophysin expression as prognostic factor for survival in colorectal carcinomas[J].Rom J Morphol Embryol,2017,58(4):1409-1415.
[19]朱旭红,张萍淑,程赞赞,等.突触可塑性相关蛋白及其与临床疾病的关系[J].华北理工大学学报(医学版),2017,19(3):237-241.
[20]Stroemer RP,Kent TA,Hulsebosch CE.Neocortical neural sprouting,synaptogenesis,and behavioral recovery after neocortical infarction in rats[J].Stroke,1995,26(11):2135-2144.
[21]Madinier A,Bertrand N,Mossiat C,et al.Microglial involvement in neuroplastic changes following focal brain ischemia in rats[J].PLoS One,2013,4(12):e8101.
[22]Yi W,Xu NG,Wang GB.Experimental study on effects of electro-acupuncture in improving synaptic plasticity in focal cerebral ischemia rats[J].Zhongguo Zhong Xi Yi Jie He Za Zhi,2006,26(8):710-714.
[23]Xia WG,Zheng CJ,Zhang X,et al.Effects of"nourishing liver and kidney"acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats[J].J Huazhong Univ Sci Technolog Med Sci,2017,37(2):271-278.
[24]陈鹏,张大雁,吴思苇,等.电针结合天麻素增加局灶性脑缺血大鼠额叶皮质生长相关蛋白-43以及突触素的免疫组化表达[J].医学理论与实践,2017,30(1):1-3.
[25]赵嘉培,黄丹霞,黄赛娥,等.电针“曲池”和“足三里”对脑缺血大鼠皮质突触素、脑源性神经营养因子表达的影响[J].中国动脉硬化杂志,2017,25(11):1099-1106.
[26]Coggins PJ,Zwiers H.B-50(GAP-43):biochemistry and functional neurochemistry of a neuron-specific phosphorprotein[J].J Neurochem,1991,56(4):1095-1106.
[27]Zhu X,Wang P,Liu H,et al.Changes and Significance of SYP and GAP-43 Expression in the Hippocampus of CIH Rats[J].Int J Med Sci,2019,16(3):394-402.
[28]Martins CW,de Melo Rodrigues LC,Nitsche MA,et al.AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression[J].Behav Brain Res,2019,362:208-212.
[29]Nemes AD,Ayasoufi K,Ying Z,et al.Growth Associated Protein 43(GAP-43)as a Novel Target for the Diagnosis,Treatment and Prevention of Epileptogenesis[J].Sci Rep,2017,7(1):17702.
[30]Han XF,Zhang Y,Xiong LL,et al.Erratum to:Lentiviral-Mediated Netrin-1 Overexpression Improves Motor and Sensory Functions in SCT Rats Associated with SYP and GAP-43 Expressions[J].Mol Neurobiol,2017,54(3):1698.
[31]Gorup D,Boha?ek I,Mili?evi?T,et al.Increased expression and colocalization of GAP43 and CASP3after brain ischemic lesion in mouse[J].Neurosci Lett,2015,597:176-182.
[32]石旺清,郑关毅,陈晓东,等.大鼠脑缺血/再灌注后bFGF和GAP-43的表达与神经再生[J].中国应用生理学杂志,2013,29(1):63-67.
[33]张鹏飞,徐成成,李文磊,等.电针对局灶性脑缺血大鼠10号染色体同源丢失性磷酸酶张力蛋白和神经生长相关蛋白-43表达的影响[J].中国康复理论与实践,2015,21(1):35-38.
[34]卿鹏,柴铁劬,丁红梅,等.双侧电针结合康复训练对局灶性脑缺血/再灌注损伤大鼠海马CA3区神经生长相关蛋白43及突触素表达的影响[J].针刺研究,2016,41(4):314-320.
[35]刘斐雯,俞坤强,彭洪卫,等.电针百会、神庭穴对局灶性脑缺血再灌注大鼠学习记忆能力及海马区GAP-43蛋白表达的影响[J].中国中医急症,2016,25(2):189-192,207.
[36]周元成,吴新贵,肖贻财.电针刺激“足三里”和“内关”对脑梗死大鼠GAP-43表达的影响[J].中国针灸,2011,31(1):55-59.
[37]张晨茜,储浩然,程红亮,等.针刺风池、风府穴对缺血性脑卒中患者血浆内皮素的影响[J].上海针灸杂志,2012,31(1):15-17.
[38]徐佳,徐鸣曙.电针对大鼠脑缺血-再灌注过程中体感诱发电位P1-N1、N1-P2峰峰值变化的影响[J].上海针灸杂志,2010,29(8):542-545.
[39]秦彦强,孙忠人,魏庆双,等.针刺风池穴预处理对脑梗死大鼠的缺血耐受现象研究[J].针灸临床杂志,2015,31(9):65-68.