电针“阳陵泉”—“足三里”累积镇痛效应与海马—下丘脑神经元可塑性的研究
|
摘要
针灸可有效地缓解急慢性疼痛,针刺治疗急性疼痛可产生良好的即时效应,要巩固疗效,需要多次的治疗;对于慢性疼痛,需要更多次的重复治疗才可收到明显的效果。因此,弄清针刺产生累积效应的机制,对于进一步提高临床疗效,具有重要意义。
我们前期工作结果表明:电针镇痛累积效应出现时,大鼠的下丘脑,海马内囊泡乙酰转移酶(VAChT)、胆碱乙酰转移酶(CHAT)、蛋白激酶PKA、PKC活性明显上调,去卵巢后,雌激素的水平降低,电针对这些蛋白的表达调节的作用明显减弱。本实验从神经记忆的角度,结合突触可塑性,进一步分析针刺镇痛累加效应的作用机制。
目的:观察电针(EA)镇痛的累积效应,及其与海马和下丘脑神经元结构及功能的可塑性改变及相关蛋白表达的关系,探讨针刺缓解慢性疼痛累积效应的生物学机制。
方法:Wistar雌鼠98只,随机分为正常对照组(n=14),慢性压迫性损伤(CCI)组(n=42),去卵巢(OVX)+CCI组(n=42)。后2组又各分为不电针、EA2天(2D)和2周(2W)组,每组14例。用结扎坐骨神经诱发发慢性压迫性损伤造成慢性神经痛的模型;去除双侧卵巢加上颈背部皮下注射D-半乳糖造成神经记忆损伤的模型。用水迷宫法测试动物学习记忆能力。电针双侧“阳陵泉”-“足三里”(1-2mA,2/15Hz,30min/time)穴,1次/天(D),不同组分别电针2天(D)、2周(W)。辐射热照射测定大鼠缩腿潜伏期(paw withdrawallatency,电针组动物电针后第二天测定其后效应),以两足的差值作为痛敏分数(hyperalgesia score,HAS)。CCI后第18天灌流取材,免疫组化实验用40%的多聚甲醛灌流,电镜实验用2%的多聚甲醛和2%的戊二醛混合液灌流。用透射电子显微镜技术,观察电针后大鼠海马及下丘脑神经元突触界面相关参数(突触活性带长度、突触后致密物厚度、突触间隙、突触界面的曲率)的变化;用免疫组化法测定参与突触可塑性调节的蛋白Synaptophysin(SYN)、calcium/calmodulin-dependentprotein kinaseⅡ(CaMKⅡ)阳性产物在海马CA1、CA3区及下丘脑室旁核(paraventricular nucleus,PVN)的表达。
结果:
1)电针对CCI大鼠痛敏反应变化的影响
在单纯CCI动物上,与CCI对照组比,CCI术后第18天CCI+EA2D组的HAS变化不大(P＞0.05),而CCI+EA2W组HAS的绝对值显著减小(P＜0.05)。提示电针可以改善CCI动物的痛敏状态,并具有累积效应。在OVX+CCI复合模型动物上,趋势同上,但是与CCI+EA2W比较OVX+CCI+EA2W组HAS绝对值明显增大(P＜0.05),说明记忆损伤动物的电针累积效应较差。
2)电针对大鼠海马CA3区、下丘脑室旁核(PVN)区突触界面结构参数的影响
在单纯CCI动物上,与正常组比较,CCI术后第18天CCI组海马CA3区、下丘脑PVN区突触活性带长度、突触后致密物厚度、突触界面的曲率明显减小,突触间隙明显增大,有显著性意义(P＜0.05);说明慢性神经病理性疼痛模型大鼠上述脑区神经元突触结构产生明显病理性改变。与CCI组比较,CCI+EA2D组突触活性带长度、突触后致密物厚度、突触界面的曲率增大,突触间隙减小,但无显著性差异(P＞0.05);CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显增大,突触间隙明显减小,有显著性意义(P＜0.05)。与CCI+EA2D组比较,CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显增大,突触间隙明显减小,有显著性意(P＜0.05);提示慢性疼痛可能降低了突触间信息的传递,而电针可以调整突触界面的相关参数,从而对突触进行重塑,并有累积效应。OVX+CCI复合模型3组动物,其突触结构各参数变化的趋势同上,与CCI+EA2W比较OVX+CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显减小,突触间隙明显增大,有显著性意义(P＜0.05);记忆损伤后突触的可塑性降低,可减弱针刺镇痛的累积效应。
3)电针对海马CA1、CA3区及下丘脑室旁核(PVN)的SYN、CaMKⅡ阳性产物表达的影响:与CCI组比较,CCI+EA2W组下丘脑PVN、海马CA1、CA3区SYN、CaMKⅡ积分灰度值明显降低(表达上调;P＜0.05),而CCI+EA 2D组无明显变化。OVX+CCI+EA2W组三脑区SYN、CaMKⅡ积分灰度值明显低于OVX+CCI组(P＜0.05),而显著高于CCI+EA2W组(P＜0.05)。说明海马及下丘脑SYN、CaMKⅡ表达上调与针刺累积效应密切相关;神经记忆力的减退在一定程度上减弱针刺镇痛的累积效应。
结论:
1)电针“阳陵泉”-“足三里”可明显减轻CCI后出现的疼痛反应,且有累积效应;记忆损伤后减弱电针的累积效应;
2)电针“阳陵泉”-“足三里”可以重塑CCI引起的海马、下丘脑突触界面的变化,增大突触活性带长度、突触后致密物厚度、突触界面的曲率、减小突触间隙,增强突触间信息的传递,并且有累积效应;记忆损伤使突触的可塑性下降,降低了突触间信息的传递,影响了大脑对针刺信息的记忆,从而减弱电针的累积效应。
3)电针“阳陵泉”-“足三里”可以上调大鼠海马和下丘脑组织中SYN、CaMKⅡ表达,且有累积效应,与动物神经记忆能力有密切联系。因此,重复电针“阳陵泉”-“足三里”穴可以减轻慢性痛,并有累积效应。海马及下丘脑SYN、CaMKⅡ表达上调与针刺累积效应密切相关;而记忆损伤后神经元可塑性下降,影响了这种累积效应。本实验的创新点即从神经记忆的角度,结合突触可塑性,分析电针“阳陵泉”-“足三里”镇痛累加效应的作用机制。
Acupuncture can alleviate both acute and chronic pain effectively,one acupuncture treatment of acute disease can achieve a good and immediate therapeutic effect.In order to strengthen and obtain a reliable clinical efficacy,repeated treatment is necessary,particularly for chronic conditions.The research on the cumulative effect of repeated acupuncture treatment possesses an important significance.
Our research results have revealed that when there is a EA-induced ccumulative analgesic effect,the expression of hypothalamic and hippocampal neuronal vesicles acetyltransferase (VAChT),choline acetyltransferase(ChAT),Protein kinase C(PKC) and Protein kinase A(PKA) increased.The memory impairment caused by ovariectomy(OVX) may weaken the effects of acupuncture.This experiment from the perspective of neural memory,combined with synaptic plasticity,further analyzes the mechanism of cumulative effects of acupuncture analgesia.
Objectives:To observe the cumulative analgesic effect of electroacupuncture(EA) and to analyze its relation to the plasticity of hippocampal and hypothalamic neurons in chronic neurophathic pain rats,so as to explore its underlying biological mechanism of acupuncture in alleviating chronic pain.
Methods:A total of 98 Wistar rats were randomized into control,CCI,CCI+EA 2 day(D), CCI+EA2 week(W),OVX+CCI,OVX+CCI+EA2D and OVX+CCI+EA2W groups,with 14 cases respectively.For rats of the latter 3 groups,subcutaneous injection of D-galactose was given once daily for 7W.Morris water maze test was conducted to evaluate the rats' memory-learning ability.Chronic pain model was established by ligating the left sciatic nerve with a piece of catgut.EA(2/15Hz,1-2 mA) was applied to bilateral "Yanglingquan(GB 34)"-"Zusanli (ST 36)",for 30minutes,once daily for 2 days and for 2 weeks respectively.Radiant heat irradiation-induced paw withdrawal latency(PWL,pain threshold) was detected and PWL difference values between the two paws were used as the hyperalgesia score(HAS).Eighteen days after CCI,the rats were perfused transcardially with 4%Polyoxymethylene for immunohistochemical experiments,and 2%Polyoxymethylene plus 2%glutaraldehyde for transmission electron microscopic observation.Transmission electron microscopy was used to observe the ultrastructure changes of the synapses of the hypothalamic and hippocampal neurons,including the synaptic cleft width,thickness of the postsynaptic densities(PSD),length of the active zones and curvature of the synaptic interface after EA,Synaptophysin(SYN) and calcium/calmodulin-dependentprotein kinaseⅡ(CaMKⅡ) expression of paraventricular nucleus (PVN) of hypothalamus,and CA1 and CA3 regions of hippocampus were detected by immunohistochemistry.
Results:
1) Effect of EA on pain threshold
In simple CCI rats,compared with CCI control group,18 days after CCI,the absolute values of HAS of CCI+EA2W group reduced significantly(P＜0.05).In comparison with CCI group, the absolute values of HAS in CCI+EA2W group lowered significantly(P＜0.05),suggesting a cumulative analgesic effect after repeated EA for 2 weeks,Two days' EA had no significant changes(P＞0.05).In OVX+CCI compound model rats,the tendency of HAS was similar.In comparison with CCI +EA2W group,HAS of OVX+CCI+EA2W group was significantly higher(P＜0.05),suggesting an attenuation of the analgesic effect after OVX.
2) Effect of EA on synaptic structural parameters of neurons in the hippocampus and hypothalamus
In simple CCI rats,compared with nolmal group,18 days after CCI,the thickness of the postsynaptic densities(PSD),length of the active zones and curvature of the synaptic interface in both hippocampus and hypothalamus of CCI control group decreased significantly,and the synaptic cleft width increased significantly in CCI control group and CCI+ EA2D group(P＜0.05),Compared with CCI group,the PSD value,length of the active zones and curvature of the synaptic interface in CCI+EA2D group increased to a certain degree,and the synaptic cleft width decreased slightly.In comparison with CCI group,PSD value,length of the active zones and curvature of the synaptic interface of neuron in both hippocampus and hypothalamus in CCI+ EA2W group increased remarkably(P＜0.05),and its synaptic cleft width decreased markedly(P＜0.05),while no significant changes were found in CCI+EA2D group.It suggests that CCI may weaken the synaptic transmission of information,and EA may adjust the relevant parameters of the synaptic interface and thus to rebuild the synapse,which has a cumulative effect.In OVX+CCI rats,the tendency was similar,Compared with CCI+EA2W,the PSD, length of the active zones and curvature of the synaptic interface of hippocampal and hypothalamic neurons in OVX+CCI+EA2W group decreased considerably(P＜0.05),while the synaptic cleft width increased markedly(P＜0.05).The findings indicate that in the aged rats, the synaptic plasticity of hippocampal and hypothalamic neurons and the cumulative effect of acupuncture analgesia were weakened.
3) Effect of EA on the expression of SYN and CaMKⅡin the hippocampus CA1,CA3 and hypothalamic paraventricular nucleus(PVN)
SYN and CaMKⅡimmunoreaction positive product integral grey values(IGV) in rat hippocampal CA1,CA3 areas and hypothalamic PVN of CCI+EA2W were significantly lower (upregulation of expression) than those of CCI group(P＜0.05),but CCI+EA 2D had no significant changes.SYN and CaMKⅡof hippocampal CA1 and CA3 areas and hypothalamic PVN in OVX+CCI+EA2W group were significantly lower than those of OVX+CCI group (P＜0.05),but obviously higher than those in CCI+EA2W group(P＜0.05),suggestting that the expression of SYN and CaMKⅡin the hippocampal CA1 and CA3 areas and hypothalamic PVN was closely related to the cumulative effect of acupuncture.In rats with neural memory impairment the cumulative effect of acupuncture analgesia was reduced.
Conclusion:
1) EA of "Yanglingquan"-"Zusanli" can significantly reduce pain in CCI rots and repeated EA has a cumulative effect and OVX may lower the cumulative effect of EA.
2) EA of "Yanglingquan"-"Zusanli"can remodel the synaptic interface changes of hippocampus and hypothalamus neurons in CCI rats by increasing the PSD,length of the active zones and curvature of the synaptic interface,and reducing the synaptic deft width,and has a cumulative effect.OVX plus administration of D-galactose may reduce the synaptic plasticity of hippocampus and hypothalamus neurons and weaken the cumulative effect of EA.
3) EA of "Yanglingquan"-"Zusanli" can increase the expression of SYN and CaMKⅡin hippocampus and hypothalamus neurons and repeated EA has a cumulative effect,which may contribute to its effect in improving the synaptic plasticity.
Therefore,repeated EA of "Yanglingquan"-"Zusanli" points can relieve chronic pain,and has a cumulative effect which may be closely associated with its efficacy in upregulating the expression of presynatic SYN and intracellular CaMKⅡin hippocampal and hypothalamic neurons;and the neuronal plasticity decline by the memory impairment impacts the cumulative effect of EA.The innovation of this experiment is analysis of electro-acupuncture "Yanglingquan"-"Zusanli" cumulative effect of analgesic mechanism from the perspective of neural memory with synaptic plasticity.
我们前期工作结果表明:电针镇痛累积效应出现时,大鼠的下丘脑,海马内囊泡乙酰转移酶(VAChT)、胆碱乙酰转移酶(CHAT)、蛋白激酶PKA、PKC活性明显上调,去卵巢后,雌激素的水平降低,电针对这些蛋白的表达调节的作用明显减弱。本实验从神经记忆的角度,结合突触可塑性,进一步分析针刺镇痛累加效应的作用机制。
目的:观察电针(EA)镇痛的累积效应,及其与海马和下丘脑神经元结构及功能的可塑性改变及相关蛋白表达的关系,探讨针刺缓解慢性疼痛累积效应的生物学机制。
方法:Wistar雌鼠98只,随机分为正常对照组(n=14),慢性压迫性损伤(CCI)组(n=42),去卵巢(OVX)+CCI组(n=42)。后2组又各分为不电针、EA2天(2D)和2周(2W)组,每组14例。用结扎坐骨神经诱发发慢性压迫性损伤造成慢性神经痛的模型;去除双侧卵巢加上颈背部皮下注射D-半乳糖造成神经记忆损伤的模型。用水迷宫法测试动物学习记忆能力。电针双侧“阳陵泉”-“足三里”(1-2mA,2/15Hz,30min/time)穴,1次/天(D),不同组分别电针2天(D)、2周(W)。辐射热照射测定大鼠缩腿潜伏期(paw withdrawallatency,电针组动物电针后第二天测定其后效应),以两足的差值作为痛敏分数(hyperalgesia score,HAS)。CCI后第18天灌流取材,免疫组化实验用40%的多聚甲醛灌流,电镜实验用2%的多聚甲醛和2%的戊二醛混合液灌流。用透射电子显微镜技术,观察电针后大鼠海马及下丘脑神经元突触界面相关参数(突触活性带长度、突触后致密物厚度、突触间隙、突触界面的曲率)的变化;用免疫组化法测定参与突触可塑性调节的蛋白Synaptophysin(SYN)、calcium/calmodulin-dependentprotein kinaseⅡ(CaMKⅡ)阳性产物在海马CA1、CA3区及下丘脑室旁核(paraventricular nucleus,PVN)的表达。
结果:
1)电针对CCI大鼠痛敏反应变化的影响
在单纯CCI动物上,与CCI对照组比,CCI术后第18天CCI+EA2D组的HAS变化不大(P＞0.05),而CCI+EA2W组HAS的绝对值显著减小(P＜0.05)。提示电针可以改善CCI动物的痛敏状态,并具有累积效应。在OVX+CCI复合模型动物上,趋势同上,但是与CCI+EA2W比较OVX+CCI+EA2W组HAS绝对值明显增大(P＜0.05),说明记忆损伤动物的电针累积效应较差。
2)电针对大鼠海马CA3区、下丘脑室旁核(PVN)区突触界面结构参数的影响
在单纯CCI动物上,与正常组比较,CCI术后第18天CCI组海马CA3区、下丘脑PVN区突触活性带长度、突触后致密物厚度、突触界面的曲率明显减小,突触间隙明显增大,有显著性意义(P＜0.05);说明慢性神经病理性疼痛模型大鼠上述脑区神经元突触结构产生明显病理性改变。与CCI组比较,CCI+EA2D组突触活性带长度、突触后致密物厚度、突触界面的曲率增大,突触间隙减小,但无显著性差异(P＞0.05);CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显增大,突触间隙明显减小,有显著性意义(P＜0.05)。与CCI+EA2D组比较,CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显增大,突触间隙明显减小,有显著性意(P＜0.05);提示慢性疼痛可能降低了突触间信息的传递,而电针可以调整突触界面的相关参数,从而对突触进行重塑,并有累积效应。OVX+CCI复合模型3组动物,其突触结构各参数变化的趋势同上,与CCI+EA2W比较OVX+CCI+EA2W组突触活性带长度、突触后致密物厚度、突触界面的曲率明显减小,突触间隙明显增大,有显著性意义(P＜0.05);记忆损伤后突触的可塑性降低,可减弱针刺镇痛的累积效应。
3)电针对海马CA1、CA3区及下丘脑室旁核(PVN)的SYN、CaMKⅡ阳性产物表达的影响:与CCI组比较,CCI+EA2W组下丘脑PVN、海马CA1、CA3区SYN、CaMKⅡ积分灰度值明显降低(表达上调;P＜0.05),而CCI+EA 2D组无明显变化。OVX+CCI+EA2W组三脑区SYN、CaMKⅡ积分灰度值明显低于OVX+CCI组(P＜0.05),而显著高于CCI+EA2W组(P＜0.05)。说明海马及下丘脑SYN、CaMKⅡ表达上调与针刺累积效应密切相关;神经记忆力的减退在一定程度上减弱针刺镇痛的累积效应。
结论:
1)电针“阳陵泉”-“足三里”可明显减轻CCI后出现的疼痛反应,且有累积效应;记忆损伤后减弱电针的累积效应;
2)电针“阳陵泉”-“足三里”可以重塑CCI引起的海马、下丘脑突触界面的变化,增大突触活性带长度、突触后致密物厚度、突触界面的曲率、减小突触间隙,增强突触间信息的传递,并且有累积效应;记忆损伤使突触的可塑性下降,降低了突触间信息的传递,影响了大脑对针刺信息的记忆,从而减弱电针的累积效应。
3)电针“阳陵泉”-“足三里”可以上调大鼠海马和下丘脑组织中SYN、CaMKⅡ表达,且有累积效应,与动物神经记忆能力有密切联系。因此,重复电针“阳陵泉”-“足三里”穴可以减轻慢性痛,并有累积效应。海马及下丘脑SYN、CaMKⅡ表达上调与针刺累积效应密切相关;而记忆损伤后神经元可塑性下降,影响了这种累积效应。本实验的创新点即从神经记忆的角度,结合突触可塑性,分析电针“阳陵泉”-“足三里”镇痛累加效应的作用机制。
Acupuncture can alleviate both acute and chronic pain effectively,one acupuncture treatment of acute disease can achieve a good and immediate therapeutic effect.In order to strengthen and obtain a reliable clinical efficacy,repeated treatment is necessary,particularly for chronic conditions.The research on the cumulative effect of repeated acupuncture treatment possesses an important significance.
Our research results have revealed that when there is a EA-induced ccumulative analgesic effect,the expression of hypothalamic and hippocampal neuronal vesicles acetyltransferase (VAChT),choline acetyltransferase(ChAT),Protein kinase C(PKC) and Protein kinase A(PKA) increased.The memory impairment caused by ovariectomy(OVX) may weaken the effects of acupuncture.This experiment from the perspective of neural memory,combined with synaptic plasticity,further analyzes the mechanism of cumulative effects of acupuncture analgesia.
Objectives:To observe the cumulative analgesic effect of electroacupuncture(EA) and to analyze its relation to the plasticity of hippocampal and hypothalamic neurons in chronic neurophathic pain rats,so as to explore its underlying biological mechanism of acupuncture in alleviating chronic pain.
Methods:A total of 98 Wistar rats were randomized into control,CCI,CCI+EA 2 day(D), CCI+EA2 week(W),OVX+CCI,OVX+CCI+EA2D and OVX+CCI+EA2W groups,with 14 cases respectively.For rats of the latter 3 groups,subcutaneous injection of D-galactose was given once daily for 7W.Morris water maze test was conducted to evaluate the rats' memory-learning ability.Chronic pain model was established by ligating the left sciatic nerve with a piece of catgut.EA(2/15Hz,1-2 mA) was applied to bilateral "Yanglingquan(GB 34)"-"Zusanli (ST 36)",for 30minutes,once daily for 2 days and for 2 weeks respectively.Radiant heat irradiation-induced paw withdrawal latency(PWL,pain threshold) was detected and PWL difference values between the two paws were used as the hyperalgesia score(HAS).Eighteen days after CCI,the rats were perfused transcardially with 4%Polyoxymethylene for immunohistochemical experiments,and 2%Polyoxymethylene plus 2%glutaraldehyde for transmission electron microscopic observation.Transmission electron microscopy was used to observe the ultrastructure changes of the synapses of the hypothalamic and hippocampal neurons,including the synaptic cleft width,thickness of the postsynaptic densities(PSD),length of the active zones and curvature of the synaptic interface after EA,Synaptophysin(SYN) and calcium/calmodulin-dependentprotein kinaseⅡ(CaMKⅡ) expression of paraventricular nucleus (PVN) of hypothalamus,and CA1 and CA3 regions of hippocampus were detected by immunohistochemistry.
Results:
1) Effect of EA on pain threshold
In simple CCI rats,compared with CCI control group,18 days after CCI,the absolute values of HAS of CCI+EA2W group reduced significantly(P＜0.05).In comparison with CCI group, the absolute values of HAS in CCI+EA2W group lowered significantly(P＜0.05),suggesting a cumulative analgesic effect after repeated EA for 2 weeks,Two days' EA had no significant changes(P＞0.05).In OVX+CCI compound model rats,the tendency of HAS was similar.In comparison with CCI +EA2W group,HAS of OVX+CCI+EA2W group was significantly higher(P＜0.05),suggesting an attenuation of the analgesic effect after OVX.
2) Effect of EA on synaptic structural parameters of neurons in the hippocampus and hypothalamus
In simple CCI rats,compared with nolmal group,18 days after CCI,the thickness of the postsynaptic densities(PSD),length of the active zones and curvature of the synaptic interface in both hippocampus and hypothalamus of CCI control group decreased significantly,and the synaptic cleft width increased significantly in CCI control group and CCI+ EA2D group(P＜0.05),Compared with CCI group,the PSD value,length of the active zones and curvature of the synaptic interface in CCI+EA2D group increased to a certain degree,and the synaptic cleft width decreased slightly.In comparison with CCI group,PSD value,length of the active zones and curvature of the synaptic interface of neuron in both hippocampus and hypothalamus in CCI+ EA2W group increased remarkably(P＜0.05),and its synaptic cleft width decreased markedly(P＜0.05),while no significant changes were found in CCI+EA2D group.It suggests that CCI may weaken the synaptic transmission of information,and EA may adjust the relevant parameters of the synaptic interface and thus to rebuild the synapse,which has a cumulative effect.In OVX+CCI rats,the tendency was similar,Compared with CCI+EA2W,the PSD, length of the active zones and curvature of the synaptic interface of hippocampal and hypothalamic neurons in OVX+CCI+EA2W group decreased considerably(P＜0.05),while the synaptic cleft width increased markedly(P＜0.05).The findings indicate that in the aged rats, the synaptic plasticity of hippocampal and hypothalamic neurons and the cumulative effect of acupuncture analgesia were weakened.
3) Effect of EA on the expression of SYN and CaMKⅡin the hippocampus CA1,CA3 and hypothalamic paraventricular nucleus(PVN)
SYN and CaMKⅡimmunoreaction positive product integral grey values(IGV) in rat hippocampal CA1,CA3 areas and hypothalamic PVN of CCI+EA2W were significantly lower (upregulation of expression) than those of CCI group(P＜0.05),but CCI+EA 2D had no significant changes.SYN and CaMKⅡof hippocampal CA1 and CA3 areas and hypothalamic PVN in OVX+CCI+EA2W group were significantly lower than those of OVX+CCI group (P＜0.05),but obviously higher than those in CCI+EA2W group(P＜0.05),suggestting that the expression of SYN and CaMKⅡin the hippocampal CA1 and CA3 areas and hypothalamic PVN was closely related to the cumulative effect of acupuncture.In rats with neural memory impairment the cumulative effect of acupuncture analgesia was reduced.
Conclusion:
1) EA of "Yanglingquan"-"Zusanli" can significantly reduce pain in CCI rots and repeated EA has a cumulative effect and OVX may lower the cumulative effect of EA.
2) EA of "Yanglingquan"-"Zusanli"can remodel the synaptic interface changes of hippocampus and hypothalamus neurons in CCI rats by increasing the PSD,length of the active zones and curvature of the synaptic interface,and reducing the synaptic deft width,and has a cumulative effect.OVX plus administration of D-galactose may reduce the synaptic plasticity of hippocampus and hypothalamus neurons and weaken the cumulative effect of EA.
3) EA of "Yanglingquan"-"Zusanli" can increase the expression of SYN and CaMKⅡin hippocampus and hypothalamus neurons and repeated EA has a cumulative effect,which may contribute to its effect in improving the synaptic plasticity.
Therefore,repeated EA of "Yanglingquan"-"Zusanli" points can relieve chronic pain,and has a cumulative effect which may be closely associated with its efficacy in upregulating the expression of presynatic SYN and intracellular CaMKⅡin hippocampal and hypothalamic neurons;and the neuronal plasticity decline by the memory impairment impacts the cumulative effect of EA.The innovation of this experiment is analysis of electro-acupuncture "Yanglingquan"-"Zusanli" cumulative effect of analgesic mechanism from the perspective of neural memory with synaptic plasticity.
引文
[1]韩济生.美国国立卫生研究院(NIH)举办针灸听证会—一次历史性的盛会.针刺研究,1997,15(4):311-313
[2]杨志新.针灸临床讲座(7)坐骨神经痛.中国临床医生,2006,34(7):18-20
[3]袁鹤庭.针刺治疗糖尿病周围神经病变致手足麻木疼痛.中国针灸,2006,26(3):225-226
[4]Miller E,Maimon Y,Rosenblatt Y,et al.Delayed Effect of Acupuncture Treatment in OA ofthe Knee;ABlinded,Randomized,Controlled Trial.Evid Based Complement Alternat Med,2009 Jan 5:1-5
[5]刘万英.针刺治疗坐骨神经痛疗效观察.世界中医骨科杂志,2005,7(1):183
[6]杨薇,闰滨.针灸镇痛在德国的临床疗效观察.昆明医学院学报,2006,(3):103-105
[7]朱长山.电针治疗坐骨神经痛186例.天津中医药,2004,21(1):61
[8]张玉英,栾述智.电针疗法治疗坐骨神经痛45例.中国民间疗法,2001,9(4):16
[9]Dorsher PT,McIntosh PM.Acupuncture's effects in treating the sequelae of acute and chronic spinal cord injuries;a review of allopathic and traditional chinese medicine literature.Evid Based Complement Altemat Med,2009 Feb 25.Epub ahead of print.[pubmed]
[10]单伟,白钊.电针治疗坐骨神经痛50例.实用中医内科杂志,2009,23(1):49-50
[11]杨振海,孙俊棋,刘永文.电针结合红外线灯照射治疗坐骨神经痛61例.针灸临床杂志1999,15(1):46-47
[12]张桂芳,唐楠,王福惠.中药配合电针治疗坐骨神经痛228例临床报告.针灸临床杂志,2002,18(5):38-39
[13]杨晓勇.针刺合穴位注射治疗坐骨神经痛疗效观察.广西中医药,2005,28(2):39-40
[14]郑卫国.长针针刺结合穴位注射治疗坐骨神经痛120例.针灸临床杂志,1999,15(6):26-27
[15]王星.温针灸治疗坐骨神经痛50例.中国社区医师,2008,23(10):155
[16]王玉凤.电针治疗坐骨神经痛40例临床观察.包头医学,2008,32(3):158-159
[17]王爱琴,刘艳玲.针灸并拔罐治疗坐骨神经痛120例.中国中医急症,2008,17(9):1303
[18]Yang T,Sun F,Zhou YL.Clinical observation on acupoint sticking therapy for treatment of chronic pain of cervical intervertebral dis.Zhongguo Zhen Jiu,2009,29(3):197-9
[19]Yang DH.Effect of ear point combined therapy on plasma substance P in patients of no-aura migraine at different stages.Zhongguo Zhen Jiu,2009,29(3):189-91
[20]黄仕荣.单穴电针疗法治疗腰椎间盘突出症的再认识.中国针灸,2007,27(9):699-700
[21]Itoh K,Itoh S,Katsumi Y,et al.A pilot study on using acupuncture and transcutaneous electrical nerve stimulation to treat chronic non-specific low back pain.Complement Ther Clin Pract,2009,15(1):22-5
[22]Manheimer E,White A,Berman B,Forys K,Emst E.Meta-analysis:acupuncture for low back pain.Ann Int Med,2005,42:651-63
[23]Ezzo J,Hadhazy V,Birch S,et al.Acupuncture for osteoarthritis of the knee:a systematic review.Arthr Rheum,2001,44:819-25
[24]Trinh K,Graham N,Gross A,et al.Acupuncture for neck disorder.Spine,2007,32:236-43
[25]张慧敏,费宇彤,时宇静,等.针刺“百会”、“太阳”改善局灶性脑缺血脑微血管内皮细胞功能的动态观察.针刺研究,2006,31(2):67
[26]韩济生.影响针刺镇痛效果的若干因素,针刺研究,1994,19(3-4):1-4
[27]董志强,马飞,笪翠娣,等.累加电针提高神经痛大鼠背根神经节GDNF mRNA的表达.上海针灸杂志,2005,24(2):33-36
[28]陈丁生,朱丽霞,莫孝荣,等.电针治疗对糖尿病大鼠坐骨神Na+-K+/ATPase活性的影响.针刺研究,1999,24(3):202
[29]赵欣,于布为.疼痛机制研究进展.上海医学,2007,30(6):462-465
[30]许绍芬.神经生物学.复旦大学出版社,2006,330-335
[31]张香桐.针刺镇痛的神经生理学基础.中国科学,1978(4):465
[32]韩济生.针刺镇痛及其有关的神经通路和神经介质.生理科学进展,1984(4):294
[33]许绍芬.神经生物学.复旦大学出版社,2006,345-350
[34]Song MJ,Wang YQ,Wu GC.Additive anti-hyperalgesia of electroacupuncture and intrathecal antisense oligodeoxynucleotide to interleukin-1 receptor type Ⅰ on carrageenan-induced inflammatory pain in rats.Brain Res Bull,2009,78(6):335-41
[35]Kim H,Shim I,Yi SH,Lee H,Lim HS,Hahm DH..Warm needle acupuncture at Pungsi (GB31) has an enhanced analgesic effect on formalin-induced pain in rats.Brain Res Bull,2009,78(4-5):164-9
[36]SandkuhlerJ.Learningandmemoryinpainpathways.Pain,2000,88:113-118
[37]Mi WL,Mao-Ying QL,Liu Q,et al.Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats:involvement of the cyclooxygenase activity in the spinal cord.Brain Res Bull,2008,77(2-3):98-104
[38]张吉.针灸镇痛机制与临床.人民卫生出版社,2002:232-242
[39]Cao XD,Huang HN,Qu GL,et al.Acupuncture balanced anesthesia in china.Acupuncture Electrotherapeutics Res Int,1997,22:60-61
[40]诸毅晖,成词松,陈玉华,等.“足三里”穴位注射镇痛效应与中缝大核共存神经递质5-HT、SP表达的关系.辽宁中医杂志,2007,34(12):1816-1819
[41]黄碧兰,涂宗萍,余良主.大鼠中缝大核内一氧化氮在痛觉调制和针刺镇痛中的作用.中国临床康复,2006,10(2):187-189
[42]Yang J,Yang Y,Chen JM,et al.Effect of hypothalamic supraoptic nucleus on acupuncture analgesia in the rat.Brain Res Bull,2008,5(5):681-6
[43]Kwon Y,Kang M,Ahn C,et al.Effect of high or low frequency electroacupuncture on the cellular activity of catecholaminergic neurons in the brain stem.Acupunct Electrother Res, 2000,25(1):27-36
[44]Yang J,Yang Y,Wang CH,el al.Effect of arginine vasopressin on acupuncture analgesia in the rat.Peptides,2009,30(2):241-7
[45]Napadow V,Dhond R,Park K,et al.Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.Neuroimage,2009 Apr 1.Epub ahead of print.[pubmed]
[46]Fang J,Jin Z,Wang Y,Li K,el al.The salient characteristics of the central effects of acupuncture needling:limbic-paralimbic-neocortical network modulation.Hum Brain Mapp,2009,30(4):1196-206
[47]Zhang JH,Cao XD,Lie J,et al.Neuronal specificity of needling acupoints at same meridian:control functional magnetic resonance imaging study with electroacupuncture.Acupunct Electrother Res,2007,2(3-4):179-93
[48]Wang W,Liu L,Zhi X,et al.Study on the regulatory effect of electro-acupuncture on hegu point(LI4) in cerebral response with functional magnetic resonance imaging.Chin J Integr Med,2007,13(1):10-6
[49]Rho SW,Choi GS,Ko EJ,et al.Molecular changes in remote tissues induced by electro-acupuncture stimulation at acupoint ST36.Mol Cells,2008,5(2):178-83
[50]Hu B,Liu L,Guo CQ,et al.Effect of acupotomy lysis on SP and CCK-8 contents in hypothalamus and spinal cord in rats with transverse process syndrome of the third lumbar.Zhen Ci Yan Jiu,2008,3(1):22-5
[51]Wu MT,Sheen JM,Chuang KH,et al.Neuronal specificity of acupuncture response:an fMRI study with electroacupuncture.Neuroimage,2002,16:1028-37
[52]Chae Y,Park HJ,Hahm DH,et al.fMRI review on brain responses to acupuncture:the limitations and possibilities in traditional Korean acupuncture.Neurol Res,2007,9(1):42-8
[53]SunRQ,WangHC,WangY,etal.Effect of electroacupuncture with different frequencies on neuropathicpain rat model.ChinJpplPhysiol,2002,18:128-131
[54]HanJS.New evidence to substantiate the frequency specificity of acupuncture induce danalgesia.AcupunctureResearch,2001,26(3):224-227
[55]罗非.反复电针对慢性痛的累加治疗作用及其机制的研究.生理科学进展,1996,27(3):241-244
[56]Tian SL,Wang XY,Ding GH.Repeated electro-acupuncture attenuates chronic visceral hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat irritable bowel syndrome model.Life Sci,2008,83(9-10):356-63
[57]刘俊岭,陈淑萍,高永辉.重复电针镇痛效应的观察及其对血浆β-EP,ACTH及COR 变化的影响.针刺研究,2007,32(5):306-312
[58]Lin JG,Chen WL.Review:acupuncture analgesia in clinical trials.Am J Chin Med,2009,37(1):1-18
[1]李国彰.神经生理学.人民卫生出版社,2007,5-77
[2]白丽敏.神经解剖学.中国中医药出版社,2003,3
[3]Macias M.Injury induced dendritic plasticity in the mature central nervous system.Acta Neurobiol Exp(Wars),2008,68(2):334-46
[4]缪鸿石.康复医学理论与实践.上海科技出版社,2000,1-55
[5]孙奕,张志.海马神经元再生及可塑性与抑郁症.国际精神病学杂志,2007,34(3):144-146
[6]Katz LC,Shatz CJ.Synaptic activity and the construction of cortical circuits.Science,1996,274:1123-1133
[7]Saito Y,Song WJ,Murakami F.Preferential termination of corticorubral axons on spine-like dendritic protrusions in developing cat.J Neurosci,1997,17(22):8792-8803
[8]李澎涛.中医药诱导神经元可塑性变化对脑功能康复作用的研究展望.北京中医药大学学报,2002,25(1):1-4
[9]方燕南,王雪晶,洪华,等.电刺激促进脑梗死大鼠星形胶质细胞与神经元可塑性的重建.中国临床康复,2005,9(37):129-31
[10]李玉玲.电针对大鼠脑可塑性影响的研究进展.江西中医学院学报,2007,19(4):42-44.
[11]余曙光,罗松,韩婷,等.电针对老年性痴呆大鼠海马神经元突触形态可塑性的影响研究.中华神经医学杂志,2006,5(4):369-370
[12]罗松,余曙光,韩婷.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复,2006,27(10):187-190
[13]董洪涛,房恭.多因素AD动物模型的建立及针刺对其学习记忆功能的影响.上海中医药杂志,2002,5:44-46
[14]原淑娟,张志雄.电针对D-半乳糖致大鼠学习记忆障碍及突触改变的干预作用.江苏中医,2001,22(7):39-41
[15]杜亦旭,许能贵等.电针对不同时间段局灶性脑缺血大鼠缺血区突触界面参数的影响.新中医,2008,40(1):93-95
[16]杨胜,姜伟.运动训练对大鼠脑可塑性影响的研究进展.中国康复医学杂志,2006,21(10):953-955
[17]Eric R.Kandel,James H.Schwartz,Thomas M.Jessell.Principle of Neuroscience.McGraw-Hill,2000,1262
[18]Malenka R C,Nicoll R A.Long-term potentjatjon—a decade of progress? Science,1999,285(5435):1870-1874
[19]Malinow R,alenka R C.AMPA receptor trafficking and synaptic plasticity.Annu Rev Neurosci,2002,25:103-126
[20]Malenka R C.Synaptic plasticity and AMPA receptor trafficking.Ann N Y Acad Sci,2003,1003:1-11
[21]曾燕,梁勋厂,李熳,等.电针对吗啡戒断大鼠学习记忆及海马CA3区长时程增强损害的恢复作用.针刺研究,2004,29(4):245-251
[22]杨卓欣.于海波.电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响.广州中医药大学学报,2005,22(2):118-120
[23]Xing GG,Liu FY,Qu XX,et al.Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rots with neuropathic pain.Exp Neurol,2007,208(2):323-32
[24]Shi S H,Hayashi Y,Petralia R.S,et al.Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation.Science,1999,284(5421):1811-1816
[25]Debanne D,Daoudal G,Sourdet V,et al.Brain plasticity and ion channels.Journal of Physiology,2003,97(4-6):403-414
[26]Song I,Huganir RL.Regulation of AMPA receptors during synaptic plasticity.Trends in Neurosciences,2002,25(11):578-589
[27]P(?)rez-Ota(?)o I,Ehlers MD.Homeostatic plasticity and NMDA receptor trafficking.Trends in Neurosciences,2005,28(5):229-238
[24]Heine M,Groc L,Frischknecht R,et al.Surface mobility of postsynaptic AMPARs tunes synaptic transmission.Science,2008,320(5873):201-5
[28]Hunter RG,Bellani R,Bloss E,et al.Regulation of kainate receptor subunit mRNA by stress and corticosteroids in the rat hippocampus.PLoS ONE,2009,(1):e4328
[29]Ren,Li,Zhang,Wu A,et al.The influence of electro-acupuncture on neural plasticity in acute cerebral infarction.Neurological Research,2008,30:985-989
[30]Vlachos A,Korkotian E,Schonfeld E,et al.Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons.Neurosci,2009,29(4):1017-33
[31]田庆华,孙锦平,尹岭,等.电针大鼠足三里穴对脑干P物质基因表达的影响.中国康复理论与实践,2003,9(11):256-258
[32]李峰,范斌,周敬修.鼠尾伤害性刺激,针刺和针刺镇痛后弓状核-导水管周围灰质-延髓头端腹内侧区的NOS的变化.针刺研究,1997,22(2):55
[33]冯晶,肖咏,等.项针对脑卒中所致假性延髓麻痹患者血清VEGF和TGF—β_1的影响.针刺研究.2008,24(7):46-47
[34]许绍芬.神经生物学.复旦大学出版社,2006,386-397
[35]冯春生,王金,岳云,等.氯胺酮对大鼠海马脑片突触长时程增强效应的影响.吉林大学学报(医学版),2008,34(5):746-749
[36]Cassenaer S,Laurent G.Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts.Nature,2007,448(7154):709-13
[37]Billings G,van Rossum MC.Memory retention and Spike Timing Dependent Plasticity.J Neurophysiol,2009 Mar 18.[Epub ahead of print][pubmed]
[38]李彦平,赵欣.实用疼痛治疗学.人民卫生出版社,2005,11-30
[39]章明美,谢吉民.电针镇痛及CaCl2对小鼠脑突触体[Ca2+]i的影响.江苏中医药,2008,40(3):82-83
[40]罗爱林,金小高,张广雄,等.神经病理性疼痛大鼠脊髓突触后致密物质-95mRNA的表达.中华麻醉学杂志,2005,25(11):857-859
[41]林芮禾,李瑞锡,刘英,等.大鼠脊髓背角CGRP、IB4阳性终末与GABA能神经元之间的联系及GABABR1阳性终末的超微结构观察.神经解剖学杂志,2007,23(2):115-120
[42]Ma ZL,Zhu W,Zhang W,et al.Effect of the synaptic scaffolding protein Homerla on chronic compression of dorsal root ganglion.Ann Clin Lab Sci,2009,39(1):71-5
[43]Tan AM,Stamboulian S,Chang YW,et al.Neuropathic pain memory is maintained by Racl-regulated dendritic spine remodeling after spinal cord injury.J Neurosci,2008,28(49):13173-83
[44]WoolfCJ.Evidence for a central component of post injury pain hypersensitivity.Nature,1983,306:686-688
[45]孙雪华.痛觉过敏与学习记忆的关系.滨州医学院学报,2007,30(6):449-451
[46]邢国刚,刘风雨,姚磊,等.神经病理痛大鼠脊髓背角突触传递的长时程可塑性变化.北京大学学报(医学版),2003,35(3):226-229
[47]孙涛,宋文阁,姚尚龙,等.侧脑室注射内吗啡肽-1降低神经病理性疼痛大鼠海马和PAG IL-6 mRNA的表达.山东大学学报(医学版),2006,44(10).1028-1031
[48]Gilron I,Watson CP,Cahill CM,et al.Neuropathic pain:a practical guide for the clinician.Canadian Med Assoc J,2006,76:265-275
[1]Hidenoir Takahashi.Effects of scalp acupuncture and auricular therapy on acute herpetic pain and postherpetic neuralgia:A case series.Medical Acupuncture,2007,19(2):113-120
[2]刘俊岭,陈淑萍,高永辉,孟凡颖,王俊英.重复电针镇痛效应的观察及对下丘脑、垂体组织β-EP及ACTH含量变化的影响.世界针灸学会联合会成立20周年暨世界针灸学术大会论文摘要汇编,2007,10(20-22):160-161
[3]孟凡颖,王俊英,陈淑萍,高永辉,刘俊岭.电针“足三里-阳陵泉”镇痛效应观察及其机制的分析.世界针灸学会联合会成立20周年暨世界针灸学术大会论文摘要汇编,2007,10(20-22):156-159
[4]王俊英,陈淑萍,李燕华,孟凡颖,高永辉,刘俊岭.电针镇痛的累积效应与大鼠下丘脑、海马蛋白激酶A表达变化的观察,针刺研究,2008,33(2):80-88
[5]Bennett GJ,Xie YK.A peripheralmononeuropathy in rat that produces disorders of pain sensation like those seen in man.Pain,1988,33(1):87-107
[6]李忠仁.实验针灸学,中国中医药出版社,2003,327-329
[7]徐平,沈雪勇.经络腧穴学,高等教育出版社,2001,89-255
[8]Wang LX,Wang ZJ.Animal and cellular models of chronic pain.Advanced Drug Delivery Reviews,2003,55(8):949-965
[9]Wall PD,Melzack R.Textbook of Pain.Science Press/Harcourt Asia PTE Ltd,2001,144-146
[10]Xie YK,Zhang JM,PetersenM,et al.Functional change in dorsal root ganglion cell after chronic nerve constriction in the rat.J Neurophysiol,1995,73:1811-1820
[11]Morris RGM.Spatial localization does not require the presence of local cues.Learn Motiv,1981,2:239-260
[12]Ji C,Li Q,et al.Gossypium herbaceam Extracts Attenuate Ibotenic Acid-induced Excitotoxicity in Rat Hippocampus.Alzheimers Dis,2009,16(2):331-9
[13]章婷婷,刚君,方小铃..雌激素替代疗法的利与弊.医学与哲学,2006,27(1):46-47
[14]张以文.雌激素与阿尔茨海默病.国外医学妇产科学分册,1997,24(5):259-261
[15]田淑君,尹岭,孙锦平,等.针刺对去卵巢大鼠脑内胆碱乙酰转移酶基因表达的影响.生理学报,2004,4:498-502
[16]沈晓明,杜元灏,胡玲.调神益肾针法对更年期大鼠卵巢芳香化酶细胞色素P450mRNA表达的影响.中医杂志,2003,44(8):589-591
[17]Monteiro SC,Matte C,Bavaresco CS,et al.Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze.Neurobiol Learn Mem,2005,84:192-9
[18]Ha BJ.Oxidative stress in ovariectomy menopause and role of chondroitin sulfate.Arch Pharm Res,2004,27:867-72
[19]Gibbs RB.Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task.Horm Behav,2005,42:45-57
[20]Holschneider DP,Kumazawa T,Chen K,Shih JC.Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat.Life Sci,1998,63:155-60
[21]周玢,洪震,曾军,等.Alzheimer's病和血管性痴呆特征的比较研究.中国临床神经病学,2002,10(1):13-15.
[22]朱建华,郭开华,袁群芳,等.金雀异黄酮对去卵巢大鼠认知能力的影响.解剖学研究,2003,25(4):287-289
[23]刘进师,朱建华,林永秀,等.去卵巢后大鼠基底前脑NOS阳性神经元的变化及雌激素的作用.解剖学研究,2004,26(1):3-5.
[24]Hua X,Lei M,Zhang Y,Ding J,et al.Long-term D-galactose injection combined with ovariectomy serves as a new rodent model for Alzheimer's disease.Life Sci,2007,80(20):1897-905.
[25]Leutner S,Eckert A,Muller W E.ROS generation,lipid peroxidation and antioxidant enzyme activities in the ageing brain、journal of Neural Transmission,2001,108(8-9):955-967
[26]Inal M E,Kanbak G,Sunal E.Antiaxidant enzyme activities and malondialdehyde levels related to aging,Clinica Chimica Aeta,2001,305(1):75-80
[27]王少康,孙桂菊,张建新,等.亚急性衰老动物模型的建立及评价.东南大学学报(医学版),2002,21(3):217-9
[28]薜红丽,赵佩霞,魏睦新,等.衰老小鼠皮层NO,MDA,SOD水平变化及其相互关系的研究.中国老年学杂志,2000,20(2):89-90
[29]余资江,康朝胜,余德立.D-半乳糖诱导原代培养的海马神经元内cyclin D1的异常表达.中国老年学杂志,2007,26(18):1745-1747
[30]Hua X,Lei M,Ding J,et al.Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose:a potential contribution to Alzheimer's disease processes.Exp Neurol,2008,210(2):709-18
[31]Moult PR,Harvey J.Hormonal regulation of hippocampal dendritic morphology and synaptic plasticity.Cell Adh Migr,2008,2(4):269-75
[32]Rubio J,Qiong W,Liu X,Jiang Z,Dang H,Chen SL,Gonzales GF.Aqueous Extract of Black Maca(Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.Evid Based Complement Alternat Med.2008 Oct9.[Epub ahead of print][pubmed]
[33]杨向红,王彦青,高秀,吴根诚.电针对大鼠神经痛痛敏分数的影响.针刺研究,2002,27(1):60-63
[34]曹福元,姚开辉,殷光甫,等.电针对慢性神经源性痛大鼠痛行为反应和脊髓背角NOS的影响.针刺研究,2005,30(4):230-233
[35]Ceccarelli I,Fiorenzani P,Massafra C,Aloisi AM.Long-term ovariectomy changes formalin-induced licking in female rats:the role of estrogens..Reprod Biol Endocrinol,2003,1:24
[36]Tall JM,Stuesse SL,Cruce WL,Crisp T..Gender and the behavioral manifestations of neuropathic pain..Pharmacol Biochem Behav,2001,68(1):99-104.
[37]McEwen BS.Plasticity of the hippocampus::adaptation to chronic stress and allostatic load.Ann NY Acad Sci,2001,933:265-77
[38]孙雪华.痛觉过敏与学习记忆的关系.滨州医学院学报,2007,30(6):449-451
[1]包新民,舒斯云.大鼠脑立体定位图谱,人民卫生出版社,1991:35-47
[2]Gldner FH,et al.Increase in postsynaptic density material in optic target neuron of the rat supyachiasmatic necleus after bilateral enucleation.Neurosci Lett,1980,17:27-32.
[3]Jones DG,et al.An ultrastructrural study into the effect of pentobarbition on synaptic organization.Brain Res,1978,147:47-63
[4]章子贵,陆汉新,李振武,等.小鼠记忆保持能力与海马CA3区突触界面结构的相关性.神经科学,1995,2(3):136-140
[5]Liang A,Chen Y,Zhang W,et al.Effect of multiple-micronutrient supplementation on learning and memorizing ability of young rats and the ultra-structure in CA3 region of hippocampus of rat's brain.Wei Sheng Yan Jiu.2009,38(1):103-6
[6]Stanley EF.Presynaptic calcium channds and the depletion of synaptie cleft calcium ions.J Neurophysiol,2000,83(1):477-821
[7]高殿帅,张凤真.神经生物学基础.第二军医大学出版社,2006,19
[8]Kennedy MB.Signal-processing machines at the postsynaptic density.Science,2000,90(5492):750-754.
[9]Sheng M,Sala C.PDZ domains and the organization of supramolecular complexes.Annu Rev Neurosci,2001,24:1-29
[10]Sheng M,Hoogenraad CC.The postsynaptic architecture of excitatory synapses:a more quantitative view.Annu Rev Biochem.2007,76:823-847
[11]Kim E,Sheng M.PDZ domain proteins of synapses.Nat Rev Neurosci,2004,5:771-781
[12]Coyle JT.Glutamate and schizophrenia:beyond the dopamine hypothesis.Cell Mol Neurobiol,2006,6:365-384
[13]Heresco-Levy U,Javitt DC.The role ofN-methyl-D-aspartate(NMDA)receptor-mediated neurotransmission in the pathophysiology and therapeutics of psychiatric syndromes.Eur Neuropsychopharmacol,1998,8:141-152
[14]Meador-Woodruff JH,Clinton SM,Beneyto M,McCullumsmith RE.Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.Ann N Y Acad Sci,2003,1003:75-93
[15]Tsai G,Coyle JT.Glutamatergic mechanisms in schizophrenia.Annu Rev Pharmacol Toxicol,2002,2:165-179
[16]Chang-Gyu Hahn,Anamika Banerjee,Mattbew L,et al.The Post-Synaptic Density of Human Postmortem Brain Tissues:An Experimental Study Paradigm for Neuuopsychiatric Illnesses.PLoS ONE,2009,4(4):e5251
[17]Bartolomeis A,Fiore G.Postsynaptic density scafelding proteins at excitatory synapse and disorders of synaptic plasticity:implications for human behavior pathologies.Int Rev Neuorbiol,2004,59:221-254
[18]Bosenmund C,Rettig J,Brose N.Molecular mechanisms of active Zone function,Curt Opin Neurobiol,2003,13(5):509-519
[19]Thomas A,Blanpied,Justin M.,et al.Structural plasticity with preserved topology in the postsynaptic protein network.Proc Natl Acad Sci U S A,2008,105(34):12587-12592
[20]Choquet D,Triller A.The role of receptor diffusion in the organization of the postsynaptic membrane.Nat Rev Neurosci,2003,4:251-265
[21]Lisman J,Raghavachari S.A unified model of the presynaptic and postsynaptic changes during LTP at CA1 synapses.Sci STKE,2006,356:rell
[22]Shepherd JD,Huganir RL.The cell biology of synaptic plasticity:AMPA receptor trafficking.Annu Rev Cell Dev Biol.2007,23:613-643
[23]Murthy VN,Schikorski T,Stevens CF,Zhu Y.Inactivity produces increases in neurotransmitter release and synapse size.Neuron,2001,32(4):673-682
[24]Vrensen G.Change in size and shape of synaptic connections after visual training:An ultrastructural approach of synaptic plasticity,Brain Res,1981,218:79-97
[25]Zhang ZG,Du HY,Lu HX.Correlation between learning-memory and the cerebral synaptic structural parameters in mice.Acta Psychol Sin,1995,3:317-321
[26]Langnaese K.Protein components of a rat brain synaptic junctional protein preparations.Brain Res,1996,2:118-122
[27]Walikonis RS,Jensen ON,Mann M,et al.Identification of proteins in the postsynaptic density fraction by mass spectrometry.J Neurosci,2000,20(11):4069-80
[28]Peng J,Kim MJ,Cheng D,et al.Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry.J Biol Chem,2004,279(20):21003-11
[29 Jordan BA,Fernholz BD,Boussac M,et al.Identification and verification of novel rodent postsynaptic density proteins.Mol Cell Proteomics,2004,3(9):857-71
[30]Li Y,Wu FM.The plasticity of the postsynaptic density.Chin J Histochem Cytochem,1999,8(3):352-354
[31]Irie M.Binding of neuroligams to PSD-95.Science,1997,277:1511-1515
[32]Ganeshina O,Berry RW,Petralia RS,et al.Synapses with a segmented,completely partitioned postsynaptic density express more AMPA receptors than other axospinous synaptic junctions.Neuroscience.2004,125(3):615-23
[33]Kennedy MB.Signal-processing machines at the postsynaptic density.Science,2000,290(5492):750-4
[34]Bosenmund C,Rettig J,Brose N.Molecular mechanisms of active Zone function.Curt Opin Neurobiol,2003,13(5):509-519
[35]Dhananjay A.Wagh,Tobias M.Rasse,Esther Asan,et al.Bruchpilot,a Protein with Homology to ELKS/CAST,Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila,Neuron,2006,49(6):833-844
[36]Christian Rosenmund,Jens Rettig,Nils Brose.Molecular mechanisms of active zone function.Current Opinion in Neurobiology,2003,13(5):509-519
[37]Baron MK,Boeckers TM,Vaida B,et al.An architectural framework that may lie at the core of the postsynaptic density.Science,2006,311(5760):531-535.
[38]罗兰,陆汉新,吴馥梅.突触界面结构的定量分析法,南京大学学报(自然科学版),1990,26(4):690-694
[39]Dyson SE,Jones DG.Quantitation of terminal parameters and their inter-relationships in maturing central synapses:A perspective for experimental studies.Brain Res,1980,183:43-59
[40]项旭映,张红梅,胡能伟,等.脊髓背角Ⅱ板层长时程增强诱导及维持过程中的突触形态计量学研究.生理学报,2004,56(3):397-402
[41]斋藤基一郎.电针刺激猫“足三里”脊髓突触变化的实验形态学研究.神经解剖学杂志,1989,5(2):157
[42]穆鉴.电针对三叉神经尾核脊束核突触超微结构的影响.南京医学院学报,1981,1(2):48
[43]赵长清.电针镇痛时突触后膜厚度的变化.针剌研究,1982,7(2):127-128
[44]毕竟,张昆,王昌利.电针对三叉神经脊束核尾侧亚核胶状质内突触变化的实验形态学研究.针刺研究.1996,21(3):42-44
[45]Markram K,Gerard-Sehahn R,Sandi C.Selective learning and memeory impairments in mice deficient for polysialylated NCAM in adulthood.Neuroscience,2007,144(3):788-796
[46]Fabio Benfenati.Synatic plasticity and the neurobiology of learning and memory.Aeta Biomed,2007,78(1):58-66
[47]廉洁.复方地黄对AD大鼠学习记忆及海马CA1区神经元突触超微结构改变的实验研究.中华中医药学刊,2007,25(7):1482-1483
[48]Yildirim M,Janssen WG,Tabori NE,et al.Estrogen and Aging Affect Synaptic Distribution of Phosphorylated LIM Kinase(LIMK) in CA1 Region of Female Rat Hippocampus.Neuroscience,2008,152(2):360-370.
[49]Mukai H,Tsurugizawa T,Murakami G,et al.Rapid modulation oflong-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons.J Neurochem,2007,100:950-967
[50]Yasushi Hojo,Gen Murakam,Hideo Mukai,et al.Estrogen synthesis in the brain—Role in synaptic plasticity and memory.Molecular and Cellular Endocrinology,2008,290(1-2):31-43
[51]卢圣锋,邵欣,唐勇,等.电针促进阿尔茨海默病模型小鼠(SAMP8)海马神经元突触可塑性的神经细胞黏附机制.中国康复医学杂志,2008,27(12):1057-1060
[1]Martinez G,Di Giacomo C,Camazza ML,et al.MAP2,Synaptophysin immunostaining in rat brain and behavioralmodifications after cerebral postischemic reperfusion.Dev Neurosci,1997,19(6):457-464
[2]Daly C,Sugimori M,Moreira JE.Synaptophysin regulates clathrin independent endocytosis of synaptic vesicles.Proc Natl Acad,2000,97:6120-6125
[3]Leypoldt F,Flajolet M,Methner A.Neuronal differentiation of cultured human NTERA-2cl.D1 cells leads to increased expression of synapsins.Neurosci Lett,2002,324(1):37-40
[4]Ferreira A,Han HQ,Greegnard P,et al.Suppression of synapsin Ⅱ inhibits the formation ad maintenance of synapses in hippocampal culture.Proc Natl Acad Sci USA,1995,92:9225-9229
[5]Mullany PM,Lynch MA.Evidence for a role for synatophysin in expression of long—term potentiation Ⅰ rat dentate gyrus.Neuroreport,1998,9:2489-2491
[6]薛敏,潘贵书.韩氏针刺对海洛因依赖大鼠学习记忆及海马SYP表达的影响.中国应用生理学杂志,2007,23(4):454-456
[7]Ferer I.Neurons and their dendrites in frontotemporal dementia.Dement Geriatr Cogn Disord,1999,10:55-58
[8]Xiao N,Li S,Zhang X,et al.Effect of ephedrine on neuronal plasticity of hypoxic-ischemic brain damage in neonatal rats.Neurosci Lett,2008,435(2):99-102
[9]张燕平,刘其强,白宏英.激素对慢性脑缺血大鼠认知功能及突触素的影响.中国实用神经疾病杂志,2007,10(1):76-78
[10]Hu R,Yin CL,Wu N.Traditional Chinese herb Dihuang Yinzi(DY) plays neuroprotective and anti-dementia role in rats of ischemic brain injury.J Ethnopharmacol,2009,121(3):444-50
[11]董航,田玉科,等.吗啡耐受小鼠脊髓突触素的变化.中国临床康复,2006,0(6):85-88
[12]Sharma K,Mehra RD et al.Chronic exposure to estrogen and tamoxifen regulates synaptophysin and phosphorylated cAMP response element-binding(CREB) protein expression in CA1 of ovariectomized rat hippocampus.Brain Res.2007,1132(1):10-9
[13]余曙光,罗松,韩婷,等.电针对老年性痴呆大鼠海马神经元突触形态可塑性的影响研究.中华神经医学杂志,2006,5(4):369-370
[14]罗松,余曙光,韩婷.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复.2006,27(10):187-190
[15]董洪涛,房恭.多因素AD动物模型的建立及针刺对其学习记忆功能的影响.上海中医药杂志,2002,5:44-46
[16]原淑娟,张志雄.电针对半乳糖致大鼠学习记忆障碍及突触改变的干预作用.江 苏中医,2001,22(7):39-41
[17]Chou AK,Muhammada R,Huang SM,et al.Altered synaptophysin expression in the rat spinal cord after chronic constriction injury of sciatic nerve.Neurosci Lett,2002,333(3):155-158
[18]项红兵,招伟贤,陈敏.坐骨神经慢性压迫性损伤对大鼠脊髓星形胶质细胞增生和突触重塑的影响.中华实验外科杂志,2005,22(9):1116-1117
[19]Lisman JE,Goldring MA.Feasibility of long-term storage of graded information by the Ca~(2+)/calmodulin-dependent protein kinase molecules of the postsynaptic density.Proc Nat ZAcad Sc,1988,85(14):5320-5324
[20]Kelly MT,Crary JF,Sacktor TC.Regulation of protein kinase Mzeta sythesis by multiple kinases in long—term potentiation J Neurosci,2007,27:3439-3444.
[21]Poulsen DJ,standing D,Bullshields K,et al.Overexpression of hippocampal Ca2+/calmodulin-dependent protein kinase Ⅱ improves spatial memory.J Neurosci Res,2007,85:735-739
[22]Blaeser F,Sallders MJ,TmoIlg N,et al.Long-term memory deficits in Pavlovian fear conditioning in Ca~(2+)/ calmodulin kinase kinase alpha-deficient mice.Mol cell Biol,2006,26:9105-9115
[23]孙臣友,胡伟,等.莪术油改善慢性低氧大鼠学习与记忆能力.生理学报,2008,60(2):228-234
[24]张英,曹云霞,程瑟恒,等.巨细胞病毒感染小鼠学习记忆与CaMK Ⅱ表达的变化.实用医学杂志,2008,24(13):2202-2204
[25]FranklandP W,Ohno M,Takahashi E,et al.Pharmacological regulated Induction of silent mutations:combined pharmacological and genetic appor aches for leanring and memory.N euorscientist,2003,9:104-109
[26]Gu Z,Liu W,Yan Z.beta-amyloid Impairs AMPA receptor trafficking and function by reducing CaMKⅡ synaptic distribution.J Biol Chem,2009,284(16):10639-49
[27]Rose J,Jin SX,Craig AM.Heterosynaptic molecular dynamies:locally induced propagating synaptic accumulation of CaM kinase Ⅱ.Neuron,2009,61(3):351-8
[28]Fang L,Wu J,Lin Q,et al.Calcium-calmodulin-Dependent portein kinaseⅡ contril to spinal cord central sensitization.Neuorsci,2002,22:4196-4204
[29]Luo F,Yang C,Chen Y,et al.Reversal of chronic inflammatory pain by acute inhibition of Ca~(2+)/calmodulin-dependent protein kinase Ⅱ.J Pharmacol Exp Ther,2008,325(1):267-75
[30]Liu XG,Sandkuhler Long-term potentiation of C-fiber-evoked potentialls in the rat spinal hom is prevented by spinal N-methyl-D-asparticacid receptor blockage.Neurosci Lett,191(1-2):43
[31]Sandkuhler J,Liu X G.Induction of long—term potentiation at spinal synapses by noxious stimulation or nerve injury.Eur J Neurosei,1998,10(7):2476
[32]Klein T,Magerl W,Hopf HC,et al.Perceptual correlates of nociceptive long—term potentiation and long—term depression in humans.J Neurosci,2004,24(4):964
[33]Sandktlhlerj.Learning and memory in pain pathways.Pain,2000,88(2):113
[34]张楠,卜祥宁,方力,等.CaMKII信号转导通路在慢性痛外周和中枢感受中的作用.中国临床解剖学杂志,2008,26(3):344-347
[35]Lee SJ,Escobedo-Lozoya Y,Szatmari EM et al.Activation of CaMKⅡ in single dendritic spines during long-term potentiation.Nature.2009,458(7236):299-304
[36]Sametsky EA,Disterhoft JF,Ohno M.Autophosphorylation of alphaCaMKⅡdownregulates excitability of CA1 pyramidal neurons following synaptic stimulation.Neurobiol Learn Mem,2009 Feb 24.[Epub ahead of print].[pubmed]
[37]Sanabria H,Swulius MT,Kolodziej SJ,et al.beta CaMKII regulates actin assembly and structure.J Biol Chem,2009 Feb 10.[Epub ahead of print].[pubmed]
[38]Zeitz KP,Giese KP,Silva AJ,et al.The contribution of autophosphorylated alpha-calcium-calmodulin kinaseⅡ to injury induced Persistent pain.Neuorscience,2004,128:889-898
[39]成信之,万燕杰,曾因明.钙/钙调素依赖隆蛋白激酶Ⅱ与疼痛中枢敏感化.中国疼痛医学杂志,2008,14(1):45-47
[40]Dai Y,Wang H,Ogawa A,et al.Ca~(2+)/calmodulin-dependent protein kinase Ⅱ in the spinal cord contributes to neuropathic pain in a rat model ofmononeuropathy.Eur J Neurosci,2005,21(9):2467-2474
[2]杨志新.针灸临床讲座(7)坐骨神经痛.中国临床医生,2006,34(7):18-20
[3]袁鹤庭.针刺治疗糖尿病周围神经病变致手足麻木疼痛.中国针灸,2006,26(3):225-226
[4]Miller E,Maimon Y,Rosenblatt Y,et al.Delayed Effect of Acupuncture Treatment in OA ofthe Knee;ABlinded,Randomized,Controlled Trial.Evid Based Complement Alternat Med,2009 Jan 5:1-5
[5]刘万英.针刺治疗坐骨神经痛疗效观察.世界中医骨科杂志,2005,7(1):183
[6]杨薇,闰滨.针灸镇痛在德国的临床疗效观察.昆明医学院学报,2006,(3):103-105
[7]朱长山.电针治疗坐骨神经痛186例.天津中医药,2004,21(1):61
[8]张玉英,栾述智.电针疗法治疗坐骨神经痛45例.中国民间疗法,2001,9(4):16
[9]Dorsher PT,McIntosh PM.Acupuncture's effects in treating the sequelae of acute and chronic spinal cord injuries;a review of allopathic and traditional chinese medicine literature.Evid Based Complement Altemat Med,2009 Feb 25.Epub ahead of print.[pubmed]
[10]单伟,白钊.电针治疗坐骨神经痛50例.实用中医内科杂志,2009,23(1):49-50
[11]杨振海,孙俊棋,刘永文.电针结合红外线灯照射治疗坐骨神经痛61例.针灸临床杂志1999,15(1):46-47
[12]张桂芳,唐楠,王福惠.中药配合电针治疗坐骨神经痛228例临床报告.针灸临床杂志,2002,18(5):38-39
[13]杨晓勇.针刺合穴位注射治疗坐骨神经痛疗效观察.广西中医药,2005,28(2):39-40
[14]郑卫国.长针针刺结合穴位注射治疗坐骨神经痛120例.针灸临床杂志,1999,15(6):26-27
[15]王星.温针灸治疗坐骨神经痛50例.中国社区医师,2008,23(10):155
[16]王玉凤.电针治疗坐骨神经痛40例临床观察.包头医学,2008,32(3):158-159
[17]王爱琴,刘艳玲.针灸并拔罐治疗坐骨神经痛120例.中国中医急症,2008,17(9):1303
[18]Yang T,Sun F,Zhou YL.Clinical observation on acupoint sticking therapy for treatment of chronic pain of cervical intervertebral dis.Zhongguo Zhen Jiu,2009,29(3):197-9
[19]Yang DH.Effect of ear point combined therapy on plasma substance P in patients of no-aura migraine at different stages.Zhongguo Zhen Jiu,2009,29(3):189-91
[20]黄仕荣.单穴电针疗法治疗腰椎间盘突出症的再认识.中国针灸,2007,27(9):699-700
[21]Itoh K,Itoh S,Katsumi Y,et al.A pilot study on using acupuncture and transcutaneous electrical nerve stimulation to treat chronic non-specific low back pain.Complement Ther Clin Pract,2009,15(1):22-5
[22]Manheimer E,White A,Berman B,Forys K,Emst E.Meta-analysis:acupuncture for low back pain.Ann Int Med,2005,42:651-63
[23]Ezzo J,Hadhazy V,Birch S,et al.Acupuncture for osteoarthritis of the knee:a systematic review.Arthr Rheum,2001,44:819-25
[24]Trinh K,Graham N,Gross A,et al.Acupuncture for neck disorder.Spine,2007,32:236-43
[25]张慧敏,费宇彤,时宇静,等.针刺“百会”、“太阳”改善局灶性脑缺血脑微血管内皮细胞功能的动态观察.针刺研究,2006,31(2):67
[26]韩济生.影响针刺镇痛效果的若干因素,针刺研究,1994,19(3-4):1-4
[27]董志强,马飞,笪翠娣,等.累加电针提高神经痛大鼠背根神经节GDNF mRNA的表达.上海针灸杂志,2005,24(2):33-36
[28]陈丁生,朱丽霞,莫孝荣,等.电针治疗对糖尿病大鼠坐骨神Na+-K+/ATPase活性的影响.针刺研究,1999,24(3):202
[29]赵欣,于布为.疼痛机制研究进展.上海医学,2007,30(6):462-465
[30]许绍芬.神经生物学.复旦大学出版社,2006,330-335
[31]张香桐.针刺镇痛的神经生理学基础.中国科学,1978(4):465
[32]韩济生.针刺镇痛及其有关的神经通路和神经介质.生理科学进展,1984(4):294
[33]许绍芬.神经生物学.复旦大学出版社,2006,345-350
[34]Song MJ,Wang YQ,Wu GC.Additive anti-hyperalgesia of electroacupuncture and intrathecal antisense oligodeoxynucleotide to interleukin-1 receptor type Ⅰ on carrageenan-induced inflammatory pain in rats.Brain Res Bull,2009,78(6):335-41
[35]Kim H,Shim I,Yi SH,Lee H,Lim HS,Hahm DH..Warm needle acupuncture at Pungsi (GB31) has an enhanced analgesic effect on formalin-induced pain in rats.Brain Res Bull,2009,78(4-5):164-9
[36]SandkuhlerJ.Learningandmemoryinpainpathways.Pain,2000,88:113-118
[37]Mi WL,Mao-Ying QL,Liu Q,et al.Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats:involvement of the cyclooxygenase activity in the spinal cord.Brain Res Bull,2008,77(2-3):98-104
[38]张吉.针灸镇痛机制与临床.人民卫生出版社,2002:232-242
[39]Cao XD,Huang HN,Qu GL,et al.Acupuncture balanced anesthesia in china.Acupuncture Electrotherapeutics Res Int,1997,22:60-61
[40]诸毅晖,成词松,陈玉华,等.“足三里”穴位注射镇痛效应与中缝大核共存神经递质5-HT、SP表达的关系.辽宁中医杂志,2007,34(12):1816-1819
[41]黄碧兰,涂宗萍,余良主.大鼠中缝大核内一氧化氮在痛觉调制和针刺镇痛中的作用.中国临床康复,2006,10(2):187-189
[42]Yang J,Yang Y,Chen JM,et al.Effect of hypothalamic supraoptic nucleus on acupuncture analgesia in the rat.Brain Res Bull,2008,5(5):681-6
[43]Kwon Y,Kang M,Ahn C,et al.Effect of high or low frequency electroacupuncture on the cellular activity of catecholaminergic neurons in the brain stem.Acupunct Electrother Res, 2000,25(1):27-36
[44]Yang J,Yang Y,Wang CH,el al.Effect of arginine vasopressin on acupuncture analgesia in the rat.Peptides,2009,30(2):241-7
[45]Napadow V,Dhond R,Park K,et al.Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.Neuroimage,2009 Apr 1.Epub ahead of print.[pubmed]
[46]Fang J,Jin Z,Wang Y,Li K,el al.The salient characteristics of the central effects of acupuncture needling:limbic-paralimbic-neocortical network modulation.Hum Brain Mapp,2009,30(4):1196-206
[47]Zhang JH,Cao XD,Lie J,et al.Neuronal specificity of needling acupoints at same meridian:control functional magnetic resonance imaging study with electroacupuncture.Acupunct Electrother Res,2007,2(3-4):179-93
[48]Wang W,Liu L,Zhi X,et al.Study on the regulatory effect of electro-acupuncture on hegu point(LI4) in cerebral response with functional magnetic resonance imaging.Chin J Integr Med,2007,13(1):10-6
[49]Rho SW,Choi GS,Ko EJ,et al.Molecular changes in remote tissues induced by electro-acupuncture stimulation at acupoint ST36.Mol Cells,2008,5(2):178-83
[50]Hu B,Liu L,Guo CQ,et al.Effect of acupotomy lysis on SP and CCK-8 contents in hypothalamus and spinal cord in rats with transverse process syndrome of the third lumbar.Zhen Ci Yan Jiu,2008,3(1):22-5
[51]Wu MT,Sheen JM,Chuang KH,et al.Neuronal specificity of acupuncture response:an fMRI study with electroacupuncture.Neuroimage,2002,16:1028-37
[52]Chae Y,Park HJ,Hahm DH,et al.fMRI review on brain responses to acupuncture:the limitations and possibilities in traditional Korean acupuncture.Neurol Res,2007,9(1):42-8
[53]SunRQ,WangHC,WangY,etal.Effect of electroacupuncture with different frequencies on neuropathicpain rat model.ChinJpplPhysiol,2002,18:128-131
[54]HanJS.New evidence to substantiate the frequency specificity of acupuncture induce danalgesia.AcupunctureResearch,2001,26(3):224-227
[55]罗非.反复电针对慢性痛的累加治疗作用及其机制的研究.生理科学进展,1996,27(3):241-244
[56]Tian SL,Wang XY,Ding GH.Repeated electro-acupuncture attenuates chronic visceral hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat irritable bowel syndrome model.Life Sci,2008,83(9-10):356-63
[57]刘俊岭,陈淑萍,高永辉.重复电针镇痛效应的观察及其对血浆β-EP,ACTH及COR 变化的影响.针刺研究,2007,32(5):306-312
[58]Lin JG,Chen WL.Review:acupuncture analgesia in clinical trials.Am J Chin Med,2009,37(1):1-18
[1]李国彰.神经生理学.人民卫生出版社,2007,5-77
[2]白丽敏.神经解剖学.中国中医药出版社,2003,3
[3]Macias M.Injury induced dendritic plasticity in the mature central nervous system.Acta Neurobiol Exp(Wars),2008,68(2):334-46
[4]缪鸿石.康复医学理论与实践.上海科技出版社,2000,1-55
[5]孙奕,张志.海马神经元再生及可塑性与抑郁症.国际精神病学杂志,2007,34(3):144-146
[6]Katz LC,Shatz CJ.Synaptic activity and the construction of cortical circuits.Science,1996,274:1123-1133
[7]Saito Y,Song WJ,Murakami F.Preferential termination of corticorubral axons on spine-like dendritic protrusions in developing cat.J Neurosci,1997,17(22):8792-8803
[8]李澎涛.中医药诱导神经元可塑性变化对脑功能康复作用的研究展望.北京中医药大学学报,2002,25(1):1-4
[9]方燕南,王雪晶,洪华,等.电刺激促进脑梗死大鼠星形胶质细胞与神经元可塑性的重建.中国临床康复,2005,9(37):129-31
[10]李玉玲.电针对大鼠脑可塑性影响的研究进展.江西中医学院学报,2007,19(4):42-44.
[11]余曙光,罗松,韩婷,等.电针对老年性痴呆大鼠海马神经元突触形态可塑性的影响研究.中华神经医学杂志,2006,5(4):369-370
[12]罗松,余曙光,韩婷.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复,2006,27(10):187-190
[13]董洪涛,房恭.多因素AD动物模型的建立及针刺对其学习记忆功能的影响.上海中医药杂志,2002,5:44-46
[14]原淑娟,张志雄.电针对D-半乳糖致大鼠学习记忆障碍及突触改变的干预作用.江苏中医,2001,22(7):39-41
[15]杜亦旭,许能贵等.电针对不同时间段局灶性脑缺血大鼠缺血区突触界面参数的影响.新中医,2008,40(1):93-95
[16]杨胜,姜伟.运动训练对大鼠脑可塑性影响的研究进展.中国康复医学杂志,2006,21(10):953-955
[17]Eric R.Kandel,James H.Schwartz,Thomas M.Jessell.Principle of Neuroscience.McGraw-Hill,2000,1262
[18]Malenka R C,Nicoll R A.Long-term potentjatjon—a decade of progress? Science,1999,285(5435):1870-1874
[19]Malinow R,alenka R C.AMPA receptor trafficking and synaptic plasticity.Annu Rev Neurosci,2002,25:103-126
[20]Malenka R C.Synaptic plasticity and AMPA receptor trafficking.Ann N Y Acad Sci,2003,1003:1-11
[21]曾燕,梁勋厂,李熳,等.电针对吗啡戒断大鼠学习记忆及海马CA3区长时程增强损害的恢复作用.针刺研究,2004,29(4):245-251
[22]杨卓欣.于海波.电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响.广州中医药大学学报,2005,22(2):118-120
[23]Xing GG,Liu FY,Qu XX,et al.Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rots with neuropathic pain.Exp Neurol,2007,208(2):323-32
[24]Shi S H,Hayashi Y,Petralia R.S,et al.Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation.Science,1999,284(5421):1811-1816
[25]Debanne D,Daoudal G,Sourdet V,et al.Brain plasticity and ion channels.Journal of Physiology,2003,97(4-6):403-414
[26]Song I,Huganir RL.Regulation of AMPA receptors during synaptic plasticity.Trends in Neurosciences,2002,25(11):578-589
[27]P(?)rez-Ota(?)o I,Ehlers MD.Homeostatic plasticity and NMDA receptor trafficking.Trends in Neurosciences,2005,28(5):229-238
[24]Heine M,Groc L,Frischknecht R,et al.Surface mobility of postsynaptic AMPARs tunes synaptic transmission.Science,2008,320(5873):201-5
[28]Hunter RG,Bellani R,Bloss E,et al.Regulation of kainate receptor subunit mRNA by stress and corticosteroids in the rat hippocampus.PLoS ONE,2009,(1):e4328
[29]Ren,Li,Zhang,Wu A,et al.The influence of electro-acupuncture on neural plasticity in acute cerebral infarction.Neurological Research,2008,30:985-989
[30]Vlachos A,Korkotian E,Schonfeld E,et al.Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons.Neurosci,2009,29(4):1017-33
[31]田庆华,孙锦平,尹岭,等.电针大鼠足三里穴对脑干P物质基因表达的影响.中国康复理论与实践,2003,9(11):256-258
[32]李峰,范斌,周敬修.鼠尾伤害性刺激,针刺和针刺镇痛后弓状核-导水管周围灰质-延髓头端腹内侧区的NOS的变化.针刺研究,1997,22(2):55
[33]冯晶,肖咏,等.项针对脑卒中所致假性延髓麻痹患者血清VEGF和TGF—β_1的影响.针刺研究.2008,24(7):46-47
[34]许绍芬.神经生物学.复旦大学出版社,2006,386-397
[35]冯春生,王金,岳云,等.氯胺酮对大鼠海马脑片突触长时程增强效应的影响.吉林大学学报(医学版),2008,34(5):746-749
[36]Cassenaer S,Laurent G.Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts.Nature,2007,448(7154):709-13
[37]Billings G,van Rossum MC.Memory retention and Spike Timing Dependent Plasticity.J Neurophysiol,2009 Mar 18.[Epub ahead of print][pubmed]
[38]李彦平,赵欣.实用疼痛治疗学.人民卫生出版社,2005,11-30
[39]章明美,谢吉民.电针镇痛及CaCl2对小鼠脑突触体[Ca2+]i的影响.江苏中医药,2008,40(3):82-83
[40]罗爱林,金小高,张广雄,等.神经病理性疼痛大鼠脊髓突触后致密物质-95mRNA的表达.中华麻醉学杂志,2005,25(11):857-859
[41]林芮禾,李瑞锡,刘英,等.大鼠脊髓背角CGRP、IB4阳性终末与GABA能神经元之间的联系及GABABR1阳性终末的超微结构观察.神经解剖学杂志,2007,23(2):115-120
[42]Ma ZL,Zhu W,Zhang W,et al.Effect of the synaptic scaffolding protein Homerla on chronic compression of dorsal root ganglion.Ann Clin Lab Sci,2009,39(1):71-5
[43]Tan AM,Stamboulian S,Chang YW,et al.Neuropathic pain memory is maintained by Racl-regulated dendritic spine remodeling after spinal cord injury.J Neurosci,2008,28(49):13173-83
[44]WoolfCJ.Evidence for a central component of post injury pain hypersensitivity.Nature,1983,306:686-688
[45]孙雪华.痛觉过敏与学习记忆的关系.滨州医学院学报,2007,30(6):449-451
[46]邢国刚,刘风雨,姚磊,等.神经病理痛大鼠脊髓背角突触传递的长时程可塑性变化.北京大学学报(医学版),2003,35(3):226-229
[47]孙涛,宋文阁,姚尚龙,等.侧脑室注射内吗啡肽-1降低神经病理性疼痛大鼠海马和PAG IL-6 mRNA的表达.山东大学学报(医学版),2006,44(10).1028-1031
[48]Gilron I,Watson CP,Cahill CM,et al.Neuropathic pain:a practical guide for the clinician.Canadian Med Assoc J,2006,76:265-275
[1]Hidenoir Takahashi.Effects of scalp acupuncture and auricular therapy on acute herpetic pain and postherpetic neuralgia:A case series.Medical Acupuncture,2007,19(2):113-120
[2]刘俊岭,陈淑萍,高永辉,孟凡颖,王俊英.重复电针镇痛效应的观察及对下丘脑、垂体组织β-EP及ACTH含量变化的影响.世界针灸学会联合会成立20周年暨世界针灸学术大会论文摘要汇编,2007,10(20-22):160-161
[3]孟凡颖,王俊英,陈淑萍,高永辉,刘俊岭.电针“足三里-阳陵泉”镇痛效应观察及其机制的分析.世界针灸学会联合会成立20周年暨世界针灸学术大会论文摘要汇编,2007,10(20-22):156-159
[4]王俊英,陈淑萍,李燕华,孟凡颖,高永辉,刘俊岭.电针镇痛的累积效应与大鼠下丘脑、海马蛋白激酶A表达变化的观察,针刺研究,2008,33(2):80-88
[5]Bennett GJ,Xie YK.A peripheralmononeuropathy in rat that produces disorders of pain sensation like those seen in man.Pain,1988,33(1):87-107
[6]李忠仁.实验针灸学,中国中医药出版社,2003,327-329
[7]徐平,沈雪勇.经络腧穴学,高等教育出版社,2001,89-255
[8]Wang LX,Wang ZJ.Animal and cellular models of chronic pain.Advanced Drug Delivery Reviews,2003,55(8):949-965
[9]Wall PD,Melzack R.Textbook of Pain.Science Press/Harcourt Asia PTE Ltd,2001,144-146
[10]Xie YK,Zhang JM,PetersenM,et al.Functional change in dorsal root ganglion cell after chronic nerve constriction in the rat.J Neurophysiol,1995,73:1811-1820
[11]Morris RGM.Spatial localization does not require the presence of local cues.Learn Motiv,1981,2:239-260
[12]Ji C,Li Q,et al.Gossypium herbaceam Extracts Attenuate Ibotenic Acid-induced Excitotoxicity in Rat Hippocampus.Alzheimers Dis,2009,16(2):331-9
[13]章婷婷,刚君,方小铃..雌激素替代疗法的利与弊.医学与哲学,2006,27(1):46-47
[14]张以文.雌激素与阿尔茨海默病.国外医学妇产科学分册,1997,24(5):259-261
[15]田淑君,尹岭,孙锦平,等.针刺对去卵巢大鼠脑内胆碱乙酰转移酶基因表达的影响.生理学报,2004,4:498-502
[16]沈晓明,杜元灏,胡玲.调神益肾针法对更年期大鼠卵巢芳香化酶细胞色素P450mRNA表达的影响.中医杂志,2003,44(8):589-591
[17]Monteiro SC,Matte C,Bavaresco CS,et al.Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze.Neurobiol Learn Mem,2005,84:192-9
[18]Ha BJ.Oxidative stress in ovariectomy menopause and role of chondroitin sulfate.Arch Pharm Res,2004,27:867-72
[19]Gibbs RB.Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task.Horm Behav,2005,42:45-57
[20]Holschneider DP,Kumazawa T,Chen K,Shih JC.Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat.Life Sci,1998,63:155-60
[21]周玢,洪震,曾军,等.Alzheimer's病和血管性痴呆特征的比较研究.中国临床神经病学,2002,10(1):13-15.
[22]朱建华,郭开华,袁群芳,等.金雀异黄酮对去卵巢大鼠认知能力的影响.解剖学研究,2003,25(4):287-289
[23]刘进师,朱建华,林永秀,等.去卵巢后大鼠基底前脑NOS阳性神经元的变化及雌激素的作用.解剖学研究,2004,26(1):3-5.
[24]Hua X,Lei M,Zhang Y,Ding J,et al.Long-term D-galactose injection combined with ovariectomy serves as a new rodent model for Alzheimer's disease.Life Sci,2007,80(20):1897-905.
[25]Leutner S,Eckert A,Muller W E.ROS generation,lipid peroxidation and antioxidant enzyme activities in the ageing brain、journal of Neural Transmission,2001,108(8-9):955-967
[26]Inal M E,Kanbak G,Sunal E.Antiaxidant enzyme activities and malondialdehyde levels related to aging,Clinica Chimica Aeta,2001,305(1):75-80
[27]王少康,孙桂菊,张建新,等.亚急性衰老动物模型的建立及评价.东南大学学报(医学版),2002,21(3):217-9
[28]薜红丽,赵佩霞,魏睦新,等.衰老小鼠皮层NO,MDA,SOD水平变化及其相互关系的研究.中国老年学杂志,2000,20(2):89-90
[29]余资江,康朝胜,余德立.D-半乳糖诱导原代培养的海马神经元内cyclin D1的异常表达.中国老年学杂志,2007,26(18):1745-1747
[30]Hua X,Lei M,Ding J,et al.Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose:a potential contribution to Alzheimer's disease processes.Exp Neurol,2008,210(2):709-18
[31]Moult PR,Harvey J.Hormonal regulation of hippocampal dendritic morphology and synaptic plasticity.Cell Adh Migr,2008,2(4):269-75
[32]Rubio J,Qiong W,Liu X,Jiang Z,Dang H,Chen SL,Gonzales GF.Aqueous Extract of Black Maca(Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.Evid Based Complement Alternat Med.2008 Oct9.[Epub ahead of print][pubmed]
[33]杨向红,王彦青,高秀,吴根诚.电针对大鼠神经痛痛敏分数的影响.针刺研究,2002,27(1):60-63
[34]曹福元,姚开辉,殷光甫,等.电针对慢性神经源性痛大鼠痛行为反应和脊髓背角NOS的影响.针刺研究,2005,30(4):230-233
[35]Ceccarelli I,Fiorenzani P,Massafra C,Aloisi AM.Long-term ovariectomy changes formalin-induced licking in female rats:the role of estrogens..Reprod Biol Endocrinol,2003,1:24
[36]Tall JM,Stuesse SL,Cruce WL,Crisp T..Gender and the behavioral manifestations of neuropathic pain..Pharmacol Biochem Behav,2001,68(1):99-104.
[37]McEwen BS.Plasticity of the hippocampus::adaptation to chronic stress and allostatic load.Ann NY Acad Sci,2001,933:265-77
[38]孙雪华.痛觉过敏与学习记忆的关系.滨州医学院学报,2007,30(6):449-451
[1]包新民,舒斯云.大鼠脑立体定位图谱,人民卫生出版社,1991:35-47
[2]Gldner FH,et al.Increase in postsynaptic density material in optic target neuron of the rat supyachiasmatic necleus after bilateral enucleation.Neurosci Lett,1980,17:27-32.
[3]Jones DG,et al.An ultrastructrural study into the effect of pentobarbition on synaptic organization.Brain Res,1978,147:47-63
[4]章子贵,陆汉新,李振武,等.小鼠记忆保持能力与海马CA3区突触界面结构的相关性.神经科学,1995,2(3):136-140
[5]Liang A,Chen Y,Zhang W,et al.Effect of multiple-micronutrient supplementation on learning and memorizing ability of young rats and the ultra-structure in CA3 region of hippocampus of rat's brain.Wei Sheng Yan Jiu.2009,38(1):103-6
[6]Stanley EF.Presynaptic calcium channds and the depletion of synaptie cleft calcium ions.J Neurophysiol,2000,83(1):477-821
[7]高殿帅,张凤真.神经生物学基础.第二军医大学出版社,2006,19
[8]Kennedy MB.Signal-processing machines at the postsynaptic density.Science,2000,90(5492):750-754.
[9]Sheng M,Sala C.PDZ domains and the organization of supramolecular complexes.Annu Rev Neurosci,2001,24:1-29
[10]Sheng M,Hoogenraad CC.The postsynaptic architecture of excitatory synapses:a more quantitative view.Annu Rev Biochem.2007,76:823-847
[11]Kim E,Sheng M.PDZ domain proteins of synapses.Nat Rev Neurosci,2004,5:771-781
[12]Coyle JT.Glutamate and schizophrenia:beyond the dopamine hypothesis.Cell Mol Neurobiol,2006,6:365-384
[13]Heresco-Levy U,Javitt DC.The role ofN-methyl-D-aspartate(NMDA)receptor-mediated neurotransmission in the pathophysiology and therapeutics of psychiatric syndromes.Eur Neuropsychopharmacol,1998,8:141-152
[14]Meador-Woodruff JH,Clinton SM,Beneyto M,McCullumsmith RE.Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.Ann N Y Acad Sci,2003,1003:75-93
[15]Tsai G,Coyle JT.Glutamatergic mechanisms in schizophrenia.Annu Rev Pharmacol Toxicol,2002,2:165-179
[16]Chang-Gyu Hahn,Anamika Banerjee,Mattbew L,et al.The Post-Synaptic Density of Human Postmortem Brain Tissues:An Experimental Study Paradigm for Neuuopsychiatric Illnesses.PLoS ONE,2009,4(4):e5251
[17]Bartolomeis A,Fiore G.Postsynaptic density scafelding proteins at excitatory synapse and disorders of synaptic plasticity:implications for human behavior pathologies.Int Rev Neuorbiol,2004,59:221-254
[18]Bosenmund C,Rettig J,Brose N.Molecular mechanisms of active Zone function,Curt Opin Neurobiol,2003,13(5):509-519
[19]Thomas A,Blanpied,Justin M.,et al.Structural plasticity with preserved topology in the postsynaptic protein network.Proc Natl Acad Sci U S A,2008,105(34):12587-12592
[20]Choquet D,Triller A.The role of receptor diffusion in the organization of the postsynaptic membrane.Nat Rev Neurosci,2003,4:251-265
[21]Lisman J,Raghavachari S.A unified model of the presynaptic and postsynaptic changes during LTP at CA1 synapses.Sci STKE,2006,356:rell
[22]Shepherd JD,Huganir RL.The cell biology of synaptic plasticity:AMPA receptor trafficking.Annu Rev Cell Dev Biol.2007,23:613-643
[23]Murthy VN,Schikorski T,Stevens CF,Zhu Y.Inactivity produces increases in neurotransmitter release and synapse size.Neuron,2001,32(4):673-682
[24]Vrensen G.Change in size and shape of synaptic connections after visual training:An ultrastructural approach of synaptic plasticity,Brain Res,1981,218:79-97
[25]Zhang ZG,Du HY,Lu HX.Correlation between learning-memory and the cerebral synaptic structural parameters in mice.Acta Psychol Sin,1995,3:317-321
[26]Langnaese K.Protein components of a rat brain synaptic junctional protein preparations.Brain Res,1996,2:118-122
[27]Walikonis RS,Jensen ON,Mann M,et al.Identification of proteins in the postsynaptic density fraction by mass spectrometry.J Neurosci,2000,20(11):4069-80
[28]Peng J,Kim MJ,Cheng D,et al.Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry.J Biol Chem,2004,279(20):21003-11
[29 Jordan BA,Fernholz BD,Boussac M,et al.Identification and verification of novel rodent postsynaptic density proteins.Mol Cell Proteomics,2004,3(9):857-71
[30]Li Y,Wu FM.The plasticity of the postsynaptic density.Chin J Histochem Cytochem,1999,8(3):352-354
[31]Irie M.Binding of neuroligams to PSD-95.Science,1997,277:1511-1515
[32]Ganeshina O,Berry RW,Petralia RS,et al.Synapses with a segmented,completely partitioned postsynaptic density express more AMPA receptors than other axospinous synaptic junctions.Neuroscience.2004,125(3):615-23
[33]Kennedy MB.Signal-processing machines at the postsynaptic density.Science,2000,290(5492):750-4
[34]Bosenmund C,Rettig J,Brose N.Molecular mechanisms of active Zone function.Curt Opin Neurobiol,2003,13(5):509-519
[35]Dhananjay A.Wagh,Tobias M.Rasse,Esther Asan,et al.Bruchpilot,a Protein with Homology to ELKS/CAST,Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila,Neuron,2006,49(6):833-844
[36]Christian Rosenmund,Jens Rettig,Nils Brose.Molecular mechanisms of active zone function.Current Opinion in Neurobiology,2003,13(5):509-519
[37]Baron MK,Boeckers TM,Vaida B,et al.An architectural framework that may lie at the core of the postsynaptic density.Science,2006,311(5760):531-535.
[38]罗兰,陆汉新,吴馥梅.突触界面结构的定量分析法,南京大学学报(自然科学版),1990,26(4):690-694
[39]Dyson SE,Jones DG.Quantitation of terminal parameters and their inter-relationships in maturing central synapses:A perspective for experimental studies.Brain Res,1980,183:43-59
[40]项旭映,张红梅,胡能伟,等.脊髓背角Ⅱ板层长时程增强诱导及维持过程中的突触形态计量学研究.生理学报,2004,56(3):397-402
[41]斋藤基一郎.电针刺激猫“足三里”脊髓突触变化的实验形态学研究.神经解剖学杂志,1989,5(2):157
[42]穆鉴.电针对三叉神经尾核脊束核突触超微结构的影响.南京医学院学报,1981,1(2):48
[43]赵长清.电针镇痛时突触后膜厚度的变化.针剌研究,1982,7(2):127-128
[44]毕竟,张昆,王昌利.电针对三叉神经脊束核尾侧亚核胶状质内突触变化的实验形态学研究.针刺研究.1996,21(3):42-44
[45]Markram K,Gerard-Sehahn R,Sandi C.Selective learning and memeory impairments in mice deficient for polysialylated NCAM in adulthood.Neuroscience,2007,144(3):788-796
[46]Fabio Benfenati.Synatic plasticity and the neurobiology of learning and memory.Aeta Biomed,2007,78(1):58-66
[47]廉洁.复方地黄对AD大鼠学习记忆及海马CA1区神经元突触超微结构改变的实验研究.中华中医药学刊,2007,25(7):1482-1483
[48]Yildirim M,Janssen WG,Tabori NE,et al.Estrogen and Aging Affect Synaptic Distribution of Phosphorylated LIM Kinase(LIMK) in CA1 Region of Female Rat Hippocampus.Neuroscience,2008,152(2):360-370.
[49]Mukai H,Tsurugizawa T,Murakami G,et al.Rapid modulation oflong-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons.J Neurochem,2007,100:950-967
[50]Yasushi Hojo,Gen Murakam,Hideo Mukai,et al.Estrogen synthesis in the brain—Role in synaptic plasticity and memory.Molecular and Cellular Endocrinology,2008,290(1-2):31-43
[51]卢圣锋,邵欣,唐勇,等.电针促进阿尔茨海默病模型小鼠(SAMP8)海马神经元突触可塑性的神经细胞黏附机制.中国康复医学杂志,2008,27(12):1057-1060
[1]Martinez G,Di Giacomo C,Camazza ML,et al.MAP2,Synaptophysin immunostaining in rat brain and behavioralmodifications after cerebral postischemic reperfusion.Dev Neurosci,1997,19(6):457-464
[2]Daly C,Sugimori M,Moreira JE.Synaptophysin regulates clathrin independent endocytosis of synaptic vesicles.Proc Natl Acad,2000,97:6120-6125
[3]Leypoldt F,Flajolet M,Methner A.Neuronal differentiation of cultured human NTERA-2cl.D1 cells leads to increased expression of synapsins.Neurosci Lett,2002,324(1):37-40
[4]Ferreira A,Han HQ,Greegnard P,et al.Suppression of synapsin Ⅱ inhibits the formation ad maintenance of synapses in hippocampal culture.Proc Natl Acad Sci USA,1995,92:9225-9229
[5]Mullany PM,Lynch MA.Evidence for a role for synatophysin in expression of long—term potentiation Ⅰ rat dentate gyrus.Neuroreport,1998,9:2489-2491
[6]薛敏,潘贵书.韩氏针刺对海洛因依赖大鼠学习记忆及海马SYP表达的影响.中国应用生理学杂志,2007,23(4):454-456
[7]Ferer I.Neurons and their dendrites in frontotemporal dementia.Dement Geriatr Cogn Disord,1999,10:55-58
[8]Xiao N,Li S,Zhang X,et al.Effect of ephedrine on neuronal plasticity of hypoxic-ischemic brain damage in neonatal rats.Neurosci Lett,2008,435(2):99-102
[9]张燕平,刘其强,白宏英.激素对慢性脑缺血大鼠认知功能及突触素的影响.中国实用神经疾病杂志,2007,10(1):76-78
[10]Hu R,Yin CL,Wu N.Traditional Chinese herb Dihuang Yinzi(DY) plays neuroprotective and anti-dementia role in rats of ischemic brain injury.J Ethnopharmacol,2009,121(3):444-50
[11]董航,田玉科,等.吗啡耐受小鼠脊髓突触素的变化.中国临床康复,2006,0(6):85-88
[12]Sharma K,Mehra RD et al.Chronic exposure to estrogen and tamoxifen regulates synaptophysin and phosphorylated cAMP response element-binding(CREB) protein expression in CA1 of ovariectomized rat hippocampus.Brain Res.2007,1132(1):10-9
[13]余曙光,罗松,韩婷,等.电针对老年性痴呆大鼠海马神经元突触形态可塑性的影响研究.中华神经医学杂志,2006,5(4):369-370
[14]罗松,余曙光,韩婷.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复.2006,27(10):187-190
[15]董洪涛,房恭.多因素AD动物模型的建立及针刺对其学习记忆功能的影响.上海中医药杂志,2002,5:44-46
[16]原淑娟,张志雄.电针对半乳糖致大鼠学习记忆障碍及突触改变的干预作用.江 苏中医,2001,22(7):39-41
[17]Chou AK,Muhammada R,Huang SM,et al.Altered synaptophysin expression in the rat spinal cord after chronic constriction injury of sciatic nerve.Neurosci Lett,2002,333(3):155-158
[18]项红兵,招伟贤,陈敏.坐骨神经慢性压迫性损伤对大鼠脊髓星形胶质细胞增生和突触重塑的影响.中华实验外科杂志,2005,22(9):1116-1117
[19]Lisman JE,Goldring MA.Feasibility of long-term storage of graded information by the Ca~(2+)/calmodulin-dependent protein kinase molecules of the postsynaptic density.Proc Nat ZAcad Sc,1988,85(14):5320-5324
[20]Kelly MT,Crary JF,Sacktor TC.Regulation of protein kinase Mzeta sythesis by multiple kinases in long—term potentiation J Neurosci,2007,27:3439-3444.
[21]Poulsen DJ,standing D,Bullshields K,et al.Overexpression of hippocampal Ca2+/calmodulin-dependent protein kinase Ⅱ improves spatial memory.J Neurosci Res,2007,85:735-739
[22]Blaeser F,Sallders MJ,TmoIlg N,et al.Long-term memory deficits in Pavlovian fear conditioning in Ca~(2+)/ calmodulin kinase kinase alpha-deficient mice.Mol cell Biol,2006,26:9105-9115
[23]孙臣友,胡伟,等.莪术油改善慢性低氧大鼠学习与记忆能力.生理学报,2008,60(2):228-234
[24]张英,曹云霞,程瑟恒,等.巨细胞病毒感染小鼠学习记忆与CaMK Ⅱ表达的变化.实用医学杂志,2008,24(13):2202-2204
[25]FranklandP W,Ohno M,Takahashi E,et al.Pharmacological regulated Induction of silent mutations:combined pharmacological and genetic appor aches for leanring and memory.N euorscientist,2003,9:104-109
[26]Gu Z,Liu W,Yan Z.beta-amyloid Impairs AMPA receptor trafficking and function by reducing CaMKⅡ synaptic distribution.J Biol Chem,2009,284(16):10639-49
[27]Rose J,Jin SX,Craig AM.Heterosynaptic molecular dynamies:locally induced propagating synaptic accumulation of CaM kinase Ⅱ.Neuron,2009,61(3):351-8
[28]Fang L,Wu J,Lin Q,et al.Calcium-calmodulin-Dependent portein kinaseⅡ contril to spinal cord central sensitization.Neuorsci,2002,22:4196-4204
[29]Luo F,Yang C,Chen Y,et al.Reversal of chronic inflammatory pain by acute inhibition of Ca~(2+)/calmodulin-dependent protein kinase Ⅱ.J Pharmacol Exp Ther,2008,325(1):267-75
[30]Liu XG,Sandkuhler Long-term potentiation of C-fiber-evoked potentialls in the rat spinal hom is prevented by spinal N-methyl-D-asparticacid receptor blockage.Neurosci Lett,191(1-2):43
[31]Sandkuhler J,Liu X G.Induction of long—term potentiation at spinal synapses by noxious stimulation or nerve injury.Eur J Neurosei,1998,10(7):2476
[32]Klein T,Magerl W,Hopf HC,et al.Perceptual correlates of nociceptive long—term potentiation and long—term depression in humans.J Neurosci,2004,24(4):964
[33]Sandktlhlerj.Learning and memory in pain pathways.Pain,2000,88(2):113
[34]张楠,卜祥宁,方力,等.CaMKII信号转导通路在慢性痛外周和中枢感受中的作用.中国临床解剖学杂志,2008,26(3):344-347
[35]Lee SJ,Escobedo-Lozoya Y,Szatmari EM et al.Activation of CaMKⅡ in single dendritic spines during long-term potentiation.Nature.2009,458(7236):299-304
[36]Sametsky EA,Disterhoft JF,Ohno M.Autophosphorylation of alphaCaMKⅡdownregulates excitability of CA1 pyramidal neurons following synaptic stimulation.Neurobiol Learn Mem,2009 Feb 24.[Epub ahead of print].[pubmed]
[37]Sanabria H,Swulius MT,Kolodziej SJ,et al.beta CaMKII regulates actin assembly and structure.J Biol Chem,2009 Feb 10.[Epub ahead of print].[pubmed]
[38]Zeitz KP,Giese KP,Silva AJ,et al.The contribution of autophosphorylated alpha-calcium-calmodulin kinaseⅡ to injury induced Persistent pain.Neuorscience,2004,128:889-898
[39]成信之,万燕杰,曾因明.钙/钙调素依赖隆蛋白激酶Ⅱ与疼痛中枢敏感化.中国疼痛医学杂志,2008,14(1):45-47
[40]Dai Y,Wang H,Ogawa A,et al.Ca~(2+)/calmodulin-dependent protein kinase Ⅱ in the spinal cord contributes to neuropathic pain in a rat model ofmononeuropathy.Eur J Neurosci,2005,21(9):2467-2474