颈椎根性痛大鼠模型建立及背根节IB4~-Aδ类神经元介导机械性痛觉敏化的机制
发布时间：2018-08-06 17:49
【摘要】：颈椎根性疾病相关痛(cervical radicularpathy pain,CRP)是现代高压力办公室工作带来的越发普遍的职业性疾病,严重影响人们生活质量并且具有自发性加重的特点。与腰背痛相比,CRP患者并无承重障碍的症状,而97.5%患者是以慢性疼痛原因就诊,包括长期自发性疼痛、肢体放散性疼痛,以及转动压迫颈椎椎骨关节引起的“闪电样”剧痛。由于动物颈椎椎骨关节解剖位置深,颈部神经丛交叉和分支多,动物颈椎部位手术难度大,一直缺乏模拟颈部病变的动物模型,CRP动物痛觉行为学难以观察。目前对于颈部外周神经病理性痛的发生发展机制尚不清楚。我们研究室前期建立腰背神经病理性痛大鼠模型,在体研究发现在此模型上外周损伤背根神经节(dorsol root ganglion,DRG)产生异常自发放电(spontaneous activity,SA)。在生理状态下DRG神经元少见,相反在慢性痛条件下DRG神经元呈现出大量异位SA。研究表明在单纤维记录实验中,表达与外周神经系统SA的纤维的传导速度多为A类有髓纤维,而极少有C类无髓纤维参与介导CCD模型中SA。DRG离体研究表明,损伤DRG神经元SA起源可能依赖于神经元的阈下膜电位振荡(subthreshold membrane potential oscillation,SMPO),而具有SMPO神经元往往伴随胞膜上离子通道激活及失活的改变表现出细胞膜内在性质的变化。因此,在病理性痛模型中初级感觉DRG神经元常常表现出异常细胞膜特性。兴奋的外周神经向脊髓痛觉感受区传递大量增加的痛觉传入将引起脊髓第一级突触的可塑性改变,形态学研究表明,在慢性痛条件下DRG神经元敏化伴随外周神经系统和脊髓背角神经终末上一系列激活基因表达的变化。但是对于CRP情况下DRG神经元如何发生改变及其机制尚不甚明了。以往研究表明,DRG神经元机械感觉功能参与机械痛敏。但是DRG感觉神经元有不同亚型神经元组成,承担不同感觉功能。机械敏感的神经元较不敏感神经元更易被机械性刺激造成损伤。但是目前缺乏针对疼痛模型特异DRG神经元的分类观察,外周慢性痛机制中各细胞和分子靶点也不明确。在本课题第一部分中,我们研究结果如下:(1)建立模拟临床CRP症状的大鼠模型,明确CRP模型大鼠痛行为学特征;(2)CRP大鼠模型DRG感觉神经元进行各亚型分类的电生理指标研究,找出CRP相关的重要细胞和分子靶点。首先,我们在大鼠颈椎C7/C8椎间孔,通过插入“L型”钢柱的手术,形成DRG稳定的慢性压迫损伤,模拟椎间盘疝出或椎骨关节狭窄的病理学特点。结果表明,CRP模型组动物较假手术组在术后1天就出现了双侧前足缩足痛阈明显下降。在术后4天达到最大值,并一直持续到手术后四周。接着我们观察了CRP模型动物表现的热痛敏,通过使用热光源对动物双侧前足足底皮肤造成伤害性热刺激。结果表明CRP模型动物在术后第3天出现上肢痛觉潜伏期明显缩短,但较温和。热痛缩足潜伏期的缩短可以持续到术后4周。同时,我们观察CRP动物的自发痛行为。自发痛行为测定为在一分钟内动物表现对患侧上肢体抓咬舔时间。CRP模型动物在术后1天就表现出较假手术组动物明显增加的患侧肢体的自发痛行为。在一周内达到最大值,在术后两周后自发痛行为时间缓慢下降。免疫组织化学结果表明,在CRP模型术后12小时C7和C8压迫侧DRG上表达c-Fos蛋白的神经元比例明显增加,在术后24小时达到最大值,在48小时后依然有明显区别。而在脊髓背角浅层,在DRG损伤12小时后,表达c-Fos蛋白的脊髓神经元也大量增加,在CRP模型术后24小时达到最大值,在48小时组仍然与假手术组有明显差异。研究提示,脊髓痛觉感觉神经元c-Fos蛋白表达的升高与DRG神经元的变化趋势一致。为了重复验证c-Fos蛋白的结果,我们观察CRP模型动物在5术后24小时后DRG和脊髓神经元磷酸化胞外信号相关激酶(Extracellular signal-related kinase,ERK)的表达。结果表明,在术后24小时,p ERK1/2在患侧DRG和脊髓神经元的表达都较假手术组明显升高。结果表明在CRP大鼠模型上,损伤DRG神经元早期激活,感觉神经元异常兴奋,向中枢神经系统痛觉感觉区传入增加引起脊髓背角感觉神经元兴奋,痛觉传导通路激活。DRG神经元分成Aβ大神经元,IB4~-Aδ小神经元、IB4~-和 IB4~+C类神经元。IB4~-Aδ小神经元明显较其他DRG小神经元更加兴奋。并且被认为介导自发痛行为的异常SA高度表达在IB4~-Aδ小神经元,而在CRP模型组的C-神经元没有出现任何自发电活动。IB4~-Aδ小神经元的SA与动作电位幅度一致,并且在记录中可以稳定持续发放两小时以上。结果提示CRP模型IB4~-Aδ小神经元表现明显SA。以往研究认为,IB4~-AδDRG神经元以其特殊的细胞膜柔韧机械特性介导外周的机械性触觉。在本课题的第二部分中,我们研究发现:(1)在CRP模型中IB4~-Aδ神经元的机械敏感特性;(2)介导DRG神经元机械敏感特性的离子通道机制;(3)CRP模型机械性痛觉过敏的外周镇痛靶点。我们使用微操作器在全细胞钳制的DRG的IB4~-AδDRG神经元胞体表面直接给予机械压力刺激(mechanical stimuli,MS),刺激强度控制在不对细胞膜造成任何伤害。结果表明,对照组观察到MS后出现的神经元放电。而在CRP组同样的MS刺激引起超高频的神经元放电活动,高频MS放电频率较SA频率升高10倍。IB4~-DRG神经元在刺激后仍可以维持长时间的高频放电水平。离子通道机制研究表明,在CRP模型组IB4~-Aδ神经元超极化激活的环核苷酸门控(hyperpolarization-activated cyclic nucleotide-gated,HCN)通道表达的Ih电流密度明显增加,这可能是CRP模型动物发生疼痛行为学改变和DRG、脊髓出现形态学改变的机制。CRP模型并未改变IB4~-的Aδ神经元的Ih电流反转电位。HCN通道蛋白和IB4双标荧光结果验证,HCN1和HCN3亚型在CRP模型后在IB4~-DRG神经元中表达升高,而HCN2亚型没有明显改变。HCN通道的特异性阻断剂ZD7288可以阻断CRP模型组IB4~-Aδ神经元包括SA、MS引起的高频放电的超兴奋性电活动,而对正常动作电位产生无影响。鞘内注射ZD7288组较生理盐水组反转了70%CRP模型引起的动物反射性缩足阈值的下降。而在热痛检测中ZD7288未见有明显改善热痛缩足潜伏期的效果。在自发痛行为检测中,ZD7288组较生理盐水组明显减少CRP模型动物的自发疼痛行为,单次给药镇痛作用超过12小时。上述结果表明,IB4~-Aδ神经元上HCN1和HCN3亚型高表达是CRP介导神经元超兴奋性改变的离子通道基础。ZD7288抑制CRP DRG神经元超兴奋性而不影响正常感觉神经元生理功能,为CRP治疗提供新的策略。
[Abstract]:Cervical radicularpathy pain (CRP) is the more common occupational disease caused by the work of modern high pressure office, which seriously affects people's quality of life and has the characteristic of spontaneous aggravation. Compared with back pain, CRP patients have no symptoms of hindrance, and 97.5% patients are due to chronic pain. Diagnosis, including long term spontaneous pain, limb disspread pain, and "lightning like" pain caused by rotation and compression of the cervical vertebra and joints. Because of the deep anatomical position of the cervical vertebra, the cervical plexus intersecting and branching, the operation of the cervical vertebra is difficult, the animal model of the cervical vertebra is lacking, and the CRP animal is painful. It is difficult to observe. The current mechanism of the occurrence and development of neuropathic pain in the peripheral neck is not clear. We established the model of lumbar back neuropathic pain in the early stage of our laboratory. In the body study, the abnormal spontaneous discharge (spontaneous activity, SA) produced by the Dorsol root ganglion (DRG) in this model was found in this model. DRG neurons in the physiological state are rare, and on the contrary, a large number of heterotopic SA. studies in DRG neurons under chronic pain conditions show that in the single fiber recording experiment, the conduction velocity of the fibers expressed in the peripheral nervous system SA is more than that of the a-kind of myelinated fibers, but few C like unmyelinated fibers participate in the CCD model in the CCD model, which indicates that the injured DRG is damaged. The origin of neuron SA may depend on the subthreshold membrane potential oscillation (subthreshold membrane potential oscillation, SMPO) of neurons, while the changes in the activation and inactivation of the ionic channels on the membrane of the cell often accompany the changes in the intrinsic properties of the membrane of the cell membrane. Therefore, the primary sensory DRG neurons in the pathological pain model are often expressed in the pathological pain model. The excitability of the peripheral nerve transmitted to the sensory region of the spinal cord caused by a large number of increased pain afferents will cause the plasticity of the first stage synapses in the spinal cord. Morphological studies suggest that DRG neurons sensitized to the peripheral nervous system and the dorsal horn nerve terminals of the spinal cord are associated with a series of activation genes under chronic pain conditions. But it is not clear how the DRG neuron changes and its mechanism in the case of CRP. Previous studies have shown that the mechanical sensory function of DRG neurons is involved in mechanical pain sensitivity. But the DRG sensory neurons have different subtypes of neurons and bear different sensory functions. The neurons of mechanical sensitization are more likely to be machine than the insensitive neurons. There is a lack of classified observation on the specific DRG neurons in the pain model, and the various cell and molecular targets in the peripheral chronic pain mechanism are not clear. In the first part of this subject, our results are as follows: (1) to establish the rat model of the simulated clinical CRP symptoms and to identify the behavioral characteristics of the CRP model rats; (2) C RP rat model DRG sensory neurons are used to study the electrophysiological indexes of the subtypes of the subtypes to identify the important cells and molecular targets related to CRP. First, we set up a "L" type of steel column by inserting a "L" steel column in the rat's cervical vertebra C7/C8, to form a stable chronic compression injury of DRG, and to simulate the pathological characteristics of the herniation of intervertebral disc or the stenosis of the vertebral joint. The results showed that the CRP model group had a significant decrease in the pain threshold of bilateral forefoot contraction at 1 days after the operation than the sham operation group. It reached the maximum at the 4 day after the operation and continued to the four weeks after the operation. Then we observed the thermal pain sensitivity of the CRP model animal, and caused the injury by using the hot light source to the bilateral plantar skin of the bilateral forefoot. Heat stimulation. The results showed that the latent period of the upper limb pain in the CRP model animals shortened obviously on the third day after the operation, but it was mild. The shortening of the latent period of the heat pain contraction could last to 4 weeks after the operation. At the same time, we observed the spontaneous pain behavior of the CRP animals. The spontaneous pain behavior was measured in one minute to the affected side of the extremities,.CRP The model animals showed a significant increase in the spontaneous pain of the affected side limbs in the 1 day after the operation. The maximum value was reached within one week, and the time of self pain decreased slowly after two weeks after the operation. The immunohistochemical results showed that the proportion of neurons of the c-Fos protein was expressed on the C7 and C8 pressure side DRG 12 hours after the CRP model operation. A significant increase was achieved at 24 hours after the operation, and there was a significant difference after 48 hours. In the shallow layer of the dorsal horn of the spinal cord, the spinal neurons expressing c-Fos protein increased significantly after 12 hours of DRG injury and reached the maximum at 24 hours after the CRP model, and there was still a significant difference between the 48 hour group and the sham operation group. The expression of c-Fos protein in sensory neurons was in accordance with the change trend of DRG neurons. In order to repeat the results of c-Fos protein, we observed the expression of phosphorylated extracellular signal related kinase (Extracellular signal-related kinase, ERK) in DRG and spinal neurons in CRP model animals after 24 hours after 5. The results showed that 24 after the operation. The expression of P ERK1/2 in the affected DRG and spinal cord neurons in the affected side was significantly higher than that in the sham operation group. The results showed that on the CRP rat model, the early activation of the DRG neurons, the abnormal excitement of the sensory neurons, the increase of the afferent area of the central nervous system to the pain sensation area of the central nervous system caused the excitation of the sensory neurons of the dorsal horn of the spinal cord and the activation of the.DRG God in the pain conduction pathway. It was divided into A beta neurons, IB4~-A delta neurons, IB4~- and IB4~+C neuron.IB4~-A delta neurons more excited than other DRG neurons, and the abnormal SA was highly expressed in IB4~-A Delta small neurons, while the C- God Jing Yuan in the CRP model group did not appear any self generating activity.IB4~-A Delta in the CRP model group. The SA of the small neurons is consistent with the action potential amplitude and can be steadily continued for more than two hours in the record. The results suggest that the CRP model IB4~-A delta neurons exhibit a significant SA. previous study that the IB4~-A Delta DRG neuron mediated the peripheral mechanical touch with its special cellular membrane flexibility mechanical properties. We have found that: (1) the mechanical sensitivity of IB4~-A delta neurons in the CRP model; (2) the mechanism of ion channel that mediates the mechanical sensitivity of DRG neurons; (3) the peripheral pain target of the CRP model of mechanical hyperalgesia. We use the micromanipulator to direct the machine directly to the surface of the cell body surface of the DRG IB4~-A Delta DRG neuron of the whole cell forceps. Stress stimulation (mechanical stimuli, MS), the stimulation intensity control does not cause any damage to the cell membrane. The result shows that the control group observed the neuronal discharge after MS. In the CRP group, the same MS stimulation causes the ultrahigh frequency neuron discharge, and the high-frequency MS discharge frequency is 10 times higher than the SA frequency, and the neuron can still be stimulated after the stimulation. In order to maintain a long time high frequency discharge level, the ion channel mechanism studies showed that the Ih current density in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel expressed in the CRP model group of IB4~-A delta neurons was significantly increased, which could be a painful behavioral change and DRG in CRP model animals. The mechanism.CRP model of the morphological changes in the spinal cord did not change the Ih current reversal potential.HCN channel protein and the IB4 double standard fluorescence results of the IB4~- A delta neurons. The HCN1 and HCN3 subtypes increased in IB4~-DRG neurons after the CRP model, while the HCN2 subtype did not significantly alter the specific blocker of the.HCN channel. The model group IB4~-A delta neurons include the hyperexcitability electrical activity of high frequency discharge caused by SA and MS, but no effect on the normal action potential. The intrathecal injection of ZD7288 group and the saline group reverses the decrease of the reflex threshold of the animals caused by the 70%CRP model. In the heat pain detection, there is no obvious improvement in the incubation period of the heat pain. In the test of self pain, the ZD7288 group significantly reduced the spontaneous pain behavior of the CRP model animal compared with the saline group, and the analgesic effect of the single dose was more than 12 hours. The results showed that the high expression of HCN1 and HCN3 subtypes on the IB4~-A delta neurons was the ionic channel basis of CRP mediated neuronal hyper excitability and the inhibition of CRP DRG by.ZD7288. Neurons are excitable without affecting the physiological functions of normal sensory neurons, and provide a new strategy for the treatment of CRP.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R681.5;R-332
本文编号：2168511
[Abstract]:Cervical radicularpathy pain (CRP) is the more common occupational disease caused by the work of modern high pressure office, which seriously affects people's quality of life and has the characteristic of spontaneous aggravation. Compared with back pain, CRP patients have no symptoms of hindrance, and 97.5% patients are due to chronic pain. Diagnosis, including long term spontaneous pain, limb disspread pain, and "lightning like" pain caused by rotation and compression of the cervical vertebra and joints. Because of the deep anatomical position of the cervical vertebra, the cervical plexus intersecting and branching, the operation of the cervical vertebra is difficult, the animal model of the cervical vertebra is lacking, and the CRP animal is painful. It is difficult to observe. The current mechanism of the occurrence and development of neuropathic pain in the peripheral neck is not clear. We established the model of lumbar back neuropathic pain in the early stage of our laboratory. In the body study, the abnormal spontaneous discharge (spontaneous activity, SA) produced by the Dorsol root ganglion (DRG) in this model was found in this model. DRG neurons in the physiological state are rare, and on the contrary, a large number of heterotopic SA. studies in DRG neurons under chronic pain conditions show that in the single fiber recording experiment, the conduction velocity of the fibers expressed in the peripheral nervous system SA is more than that of the a-kind of myelinated fibers, but few C like unmyelinated fibers participate in the CCD model in the CCD model, which indicates that the injured DRG is damaged. The origin of neuron SA may depend on the subthreshold membrane potential oscillation (subthreshold membrane potential oscillation, SMPO) of neurons, while the changes in the activation and inactivation of the ionic channels on the membrane of the cell often accompany the changes in the intrinsic properties of the membrane of the cell membrane. Therefore, the primary sensory DRG neurons in the pathological pain model are often expressed in the pathological pain model. The excitability of the peripheral nerve transmitted to the sensory region of the spinal cord caused by a large number of increased pain afferents will cause the plasticity of the first stage synapses in the spinal cord. Morphological studies suggest that DRG neurons sensitized to the peripheral nervous system and the dorsal horn nerve terminals of the spinal cord are associated with a series of activation genes under chronic pain conditions. But it is not clear how the DRG neuron changes and its mechanism in the case of CRP. Previous studies have shown that the mechanical sensory function of DRG neurons is involved in mechanical pain sensitivity. But the DRG sensory neurons have different subtypes of neurons and bear different sensory functions. The neurons of mechanical sensitization are more likely to be machine than the insensitive neurons. There is a lack of classified observation on the specific DRG neurons in the pain model, and the various cell and molecular targets in the peripheral chronic pain mechanism are not clear. In the first part of this subject, our results are as follows: (1) to establish the rat model of the simulated clinical CRP symptoms and to identify the behavioral characteristics of the CRP model rats; (2) C RP rat model DRG sensory neurons are used to study the electrophysiological indexes of the subtypes of the subtypes to identify the important cells and molecular targets related to CRP. First, we set up a "L" type of steel column by inserting a "L" steel column in the rat's cervical vertebra C7/C8, to form a stable chronic compression injury of DRG, and to simulate the pathological characteristics of the herniation of intervertebral disc or the stenosis of the vertebral joint. The results showed that the CRP model group had a significant decrease in the pain threshold of bilateral forefoot contraction at 1 days after the operation than the sham operation group. It reached the maximum at the 4 day after the operation and continued to the four weeks after the operation. Then we observed the thermal pain sensitivity of the CRP model animal, and caused the injury by using the hot light source to the bilateral plantar skin of the bilateral forefoot. Heat stimulation. The results showed that the latent period of the upper limb pain in the CRP model animals shortened obviously on the third day after the operation, but it was mild. The shortening of the latent period of the heat pain contraction could last to 4 weeks after the operation. At the same time, we observed the spontaneous pain behavior of the CRP animals. The spontaneous pain behavior was measured in one minute to the affected side of the extremities,.CRP The model animals showed a significant increase in the spontaneous pain of the affected side limbs in the 1 day after the operation. The maximum value was reached within one week, and the time of self pain decreased slowly after two weeks after the operation. The immunohistochemical results showed that the proportion of neurons of the c-Fos protein was expressed on the C7 and C8 pressure side DRG 12 hours after the CRP model operation. A significant increase was achieved at 24 hours after the operation, and there was a significant difference after 48 hours. In the shallow layer of the dorsal horn of the spinal cord, the spinal neurons expressing c-Fos protein increased significantly after 12 hours of DRG injury and reached the maximum at 24 hours after the CRP model, and there was still a significant difference between the 48 hour group and the sham operation group. The expression of c-Fos protein in sensory neurons was in accordance with the change trend of DRG neurons. In order to repeat the results of c-Fos protein, we observed the expression of phosphorylated extracellular signal related kinase (Extracellular signal-related kinase, ERK) in DRG and spinal neurons in CRP model animals after 24 hours after 5. The results showed that 24 after the operation. The expression of P ERK1/2 in the affected DRG and spinal cord neurons in the affected side was significantly higher than that in the sham operation group. The results showed that on the CRP rat model, the early activation of the DRG neurons, the abnormal excitement of the sensory neurons, the increase of the afferent area of the central nervous system to the pain sensation area of the central nervous system caused the excitation of the sensory neurons of the dorsal horn of the spinal cord and the activation of the.DRG God in the pain conduction pathway. It was divided into A beta neurons, IB4~-A delta neurons, IB4~- and IB4~+C neuron.IB4~-A delta neurons more excited than other DRG neurons, and the abnormal SA was highly expressed in IB4~-A Delta small neurons, while the C- God Jing Yuan in the CRP model group did not appear any self generating activity.IB4~-A Delta in the CRP model group. The SA of the small neurons is consistent with the action potential amplitude and can be steadily continued for more than two hours in the record. The results suggest that the CRP model IB4~-A delta neurons exhibit a significant SA. previous study that the IB4~-A Delta DRG neuron mediated the peripheral mechanical touch with its special cellular membrane flexibility mechanical properties. We have found that: (1) the mechanical sensitivity of IB4~-A delta neurons in the CRP model; (2) the mechanism of ion channel that mediates the mechanical sensitivity of DRG neurons; (3) the peripheral pain target of the CRP model of mechanical hyperalgesia. We use the micromanipulator to direct the machine directly to the surface of the cell body surface of the DRG IB4~-A Delta DRG neuron of the whole cell forceps. Stress stimulation (mechanical stimuli, MS), the stimulation intensity control does not cause any damage to the cell membrane. The result shows that the control group observed the neuronal discharge after MS. In the CRP group, the same MS stimulation causes the ultrahigh frequency neuron discharge, and the high-frequency MS discharge frequency is 10 times higher than the SA frequency, and the neuron can still be stimulated after the stimulation. In order to maintain a long time high frequency discharge level, the ion channel mechanism studies showed that the Ih current density in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel expressed in the CRP model group of IB4~-A delta neurons was significantly increased, which could be a painful behavioral change and DRG in CRP model animals. The mechanism.CRP model of the morphological changes in the spinal cord did not change the Ih current reversal potential.HCN channel protein and the IB4 double standard fluorescence results of the IB4~- A delta neurons. The HCN1 and HCN3 subtypes increased in IB4~-DRG neurons after the CRP model, while the HCN2 subtype did not significantly alter the specific blocker of the.HCN channel. The model group IB4~-A delta neurons include the hyperexcitability electrical activity of high frequency discharge caused by SA and MS, but no effect on the normal action potential. The intrathecal injection of ZD7288 group and the saline group reverses the decrease of the reflex threshold of the animals caused by the 70%CRP model. In the heat pain detection, there is no obvious improvement in the incubation period of the heat pain. In the test of self pain, the ZD7288 group significantly reduced the spontaneous pain behavior of the CRP model animal compared with the saline group, and the analgesic effect of the single dose was more than 12 hours. The results showed that the high expression of HCN1 and HCN3 subtypes on the IB4~-A delta neurons was the ionic channel basis of CRP mediated neuronal hyper excitability and the inhibition of CRP DRG by.ZD7288. Neurons are excitable without affecting the physiological functions of normal sensory neurons, and provide a new strategy for the treatment of CRP.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R681.5;R-332
【相似文献】
相关期刊论文 前10条
1 陈会丛;侯金才;李澎涛;潘彦舒;华茜;洪庆涛;杜欢;王筠;;粒细胞集落刺激因子对氧糖剥夺后培养神经元的影响[J];现代生物医学进展;2008年07期
2 卢习;范力;邵虹;段明慧;陈树林;赵善廷;;摇晃蛋白引起神经元分枝并促进树突发育[J];中国免疫学杂志;2014年02期
3 伍亚明;神经元对损伤的反应[J];中国脊柱脊髓杂志;1994年04期
4 杨青峰，廖维宏，丁珍明，范维珂;胞体型神经微丝单抗的研制[J];第三军医大学学报;1995年01期
5 张云东,朱佩芳,王正国,周继红,许民辉,邹咏文,黄显凯,粟永萍,赵继宗;培养大鼠下丘脑CRH神经元生长规律研究[J];创伤外科杂志;2004年01期
6 甘思德;神经元胞浆转运和分子信息递传(续)[J];生理科学;1982年06期
7 周文华,张富强,杨国栋;复吸的神经网络、神经元适应和复吸模型[J];中国药物依赖性杂志;2001年01期
8 邵宁生，王会信，，周廷冲;成纤维细胞生长因子对神经元的营养作用[J];生理科学进展;1994年01期
9 甘思德;神经元胞浆转运和分子信息传递[J];生理科学;1982年05期
10 王廷华,吴良芳,廖得阳;神经元生长发育的调控机制[J];昆明医学院学报;2002年01期
相关会议论文 前7条
1 刘深泉;姚良瑾;覃秋菊;吕凡;杨志华;;神经元的形态识别和电位发放特性[A];第十二届全国非线性振动暨第九届全国非线性动力学和运动稳定性学术会议论文集[C];2009年
2 李娟;陈熔;刘晓燕;谢华富;何涛;;CCK_8与EGF在小鼠神经元中的协同作用研究[A];第九届西南三省一市生物化学与分子生物学学术交流会论文集[C];2008年
3 刘淑红;吕艺;葛学铭;范明;;中枢和外周神经损伤后再生早期神经元胞体基因表达的差异[A];中国生理学会第21届全国代表大会暨学术会议论文摘要汇编[C];2002年
4 彭小清;谢益宽;;损伤神经元膜外负电性增加提高神经元的兴奋性[A];中国生理学会第21届全国代表大会暨学术会议论文摘要汇编[C];2002年
5 邵金贵;忻国妹;;人胎消化系统氮能神经元发育的研究[A];2003’离子通道、受体与信号转导专题研讨会专辑[C];2003年
6 霍福权;汪静;李云庆;陈涛;韩峰;唐敬师;;腹外侧眶皮层GABA能神经元表达5-HT1A受体[A];中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会论文摘要汇编[C];2005年
7 袁秉祥;;心脏浅表神经元的研究进展[A];中国药理学会第八次全国代表大会暨全国药理学术会议论文摘要汇编[C];2002年
相关博士学位论文 前10条
1 王丽;伏隔核GABA能神经元对可卡因环境相关记忆的调控作用及其神经环路机制研究[D];复旦大学;2014年
2 刘大路;颈椎根性痛大鼠模型建立及背根节IB4~-Aδ类神经元介导机械性痛觉敏化的机制[D];第四军医大学;2016年
3 黄维;大鼠三叉神经中脑核神经元胞体分泌的初步研究[D];第三军医大学;2010年
4 杨志军;大鼠脑内星形胶质细胞对渗透压改变的反应及其和神经元相互关系的形态学研究[D];第四军医大学;2002年
5 赵东芹;大鼠下丘脑前部—延髓内脏中枢参与束缚—浸水应激反应的神经元类型及突触可塑性[D];山东师范大学;2011年
6 张伟伟;神经营养因子和骨骼肌对DRG神经元生长的调节作用[D];山东大学;2013年
7 邢自力;NAD~+对神经元氧糖剥夺损伤的作用研究[D];复旦大学;2007年
8 熊巍;钙离子和蛋白激酶A对背根神经节神经元胞体囊泡转运过程的调控[D];中国科学院研究生院（上海生命科学研究院）;2006年
9 闫志强;丘脑底核神经元的共振及其和多巴胺受体的关系[D];第四军医大学;2012年
10 余华荣;喹啉酸对原代培养神经元的作用及机理研究[D];重庆医科大学;2007年
相关硕士学位论文 前10条
1 朱梦婷;神经元集群自持续放电活动的仿真模型[D];南昌大学;2015年
2 曹冬青;H_2S对Angiotensin Ⅱ引起的延髓神经元活性氧水平升高和钙内流的调控[D];复旦大学;2014年
3 杨胜魁;ePet-EYFP小鼠脑干下行五羟色胺神经元电生理学、形态学及神经递质调控性研究[D];华东师范大学;2016年
4 任明举;神经元胞体的几何分类[D];华中科技大学;2014年
5 郑燕菊;状态依赖时滞多神经元递归抑制环模型的动力学[D];郑州大学;2016年
6 周丹青;LDT中CRF神经元对焦虑与睡眠的调控初探[D];浙江大学;2016年
7 王玉祥;神经元兴奋模式动力学机制研究[D];河北工业大学;2012年
8 张凤军;胰岛素样生长因子-1对背根神经节神经元谷氨酸损伤的保护作用[D];山东大学;2009年
9 徐建可;星形胶质细胞条件培养液对缺氧损伤神经元的影响[D];新乡医学院;2012年
10 王俊波;甘丙肽对IC神经元声信号处理的调制[D];华中师范大学;2003年
本文编号：2168511
本文链接：https://www.wllwen.com/yixuelunwen/jichuyixue/2168511.html
