针刺缺血性脑卒中病人外关穴fMRI脑功能成像研究
|
摘要
目的
本研究运用脑功能成像技术,观察针刺缺血性脑卒中病人外关穴对脑区的激活/负激活的特点,并观察比较其与缺血性脑卒中病人外关穴假针刺和非穴针刺、正常人外关穴针刺fMRI脑功能成像特点的差异,从不同角度来分析针刺缺血性脑卒中病人外关穴的相对特异性,为阐述针刺治疗中风的机理提供初步依据。
方法
设计：组块设计(Block设计),神经影像学研究。
时间和地点：实验于2008年10月至2010年8月在南方医院MRI影像中心完成。
伦理批注：试验方案获得广州中医药大学第一附属医院伦理委员会批准[(2008)024],并在中国临床试验网上注册(http://www.chictr.org),注册号(ChiCTR-NRC-00000255)。
被试者来源：24例缺血性脑卒中病人均来自广州中医药大学第一附属医院,通过随机数字表法,随机分为外关穴组和非穴组,每组12人。6名健康志愿者均来自南方医科大学。试验前各志愿者均签署知情同意书。
缺血性脑卒中诊断标准：中医诊断标准符合1996年国家中医药管理局脑病急症协作组刊于《北京中医药大学学报》的《中风病诊断与疗效评定诊断》(二代标准)中中风病相关标准。西医诊断标准符合中华神经科学会、中华神经外科学会于1995年在第四届全国脑血管病学术会议制订的《各类脑血管病诊断要点》中缺血性脑卒中的诊断标准。
纳入标准：①缺血性脑卒中纳入标准：a.符合上述诊断标准,且病灶以左侧基底节区为主的缺血性脑卒中患者,有典型的右侧偏身运动(上肢肌力和/或下肢肌力脑卒中临床神经功能缺损程度评分量表评分≥4分)和感觉障碍者；b.度过急性期,病情稳定者；c.饮食规律,不嗜烟、酒、茶、咖啡,睡眠正常,体型适中[18.5≤体质指数(BMI)≤23.9]；d.接受西医基础治疗(拜阿司匹林/波立维等抗血小板聚集、立普妥/舒降之等降脂稳定斑块、凯时/舒血宁/碟脉灵/凯那等改善循环等),治疗方案在试验前1个月没有改变者；e.年龄在40周岁以上,65周岁以下；f右利手。②健康志愿者纳入标准：a.年龄在21-28岁之间在校大学生,男女不限；b.平素身体健康,饮食规律,不嗜烟、酒、茶、咖啡,睡眠正常,体型适中[18.5≤体质指数(BMI)≤23.9]；c.近1个月内未接受过针刺治疗；d.体内无金属类物质(如心脏支架)；e.右利手；f无幽闭恐怖症等精神病史；g.无血友病等针刺禁忌证。
排除标准：①缺血性脑卒中排除标准：a.病程长于1年者；b.试验前1个月内接受过针刺治疗者；c.有严重心、肝、肾疾病及肿瘤者；d.严重失语,或有痴呆、幽闭恐怖症等精神病史,影响实验过程中的交流和操作者；e.妊娠、哺乳期妇女；f体内有金属类物质(如心脏支架)者；g.患有血友病等针刺禁忌证者。②健康志愿者排除标准：a.不能配合实验(如拒绝签订知情同意书及无故拒绝试验等)者；b.处于生理期内(女)。
试验过程：①各被试者(缺血性脑卒中病人或正常人)常规封闭视听至fMRI检测结束(耳塞产自美国Aearo公司,批号R5A018,眼罩产自扬州市邗江鑫华旅游用品厂,批号XHYZ-001)。②缺血性脑卒中病人随机接受外关穴和非穴针刺刺激,健康志愿者只接受外关穴针刺刺激,同一被试者先后接受假针刺和真针刺。外关穴定位：在前臂背侧,当阳池与肘尖的连线上,腕背横纹上2寸(平肘尖的肘横纹和腕掌侧横纹之间的距离为12寸),尺骨与桡骨之间处。非穴定位：与外关穴相平,手少阳三焦经与少太阳小肠经在前臂循行线上连线的中点。③被试者在检查床上休息5分钟后,采用美国GE公司生产的3.0T超导MRI系统和及其标准头部线圈,首先进行T1W1三维梯度回波脉冲序列采集MR解剖图像,扫描2分42秒。检测序列为：OAX(轴位)T1FLAIR (Fluid attenuated inversion recovery),重复时间(TR)2300ms/回波时间(TE)21ms,TI(time of inversion)920ms,层厚6.0mm/间隔1.0mm；共20层,2min45s,视野(FOV)240mm×180mm/Z,矩阵320×256/NEX (number of excitations)=2, Matrix=320×256,回波链长度=9,带宽=50。④接着由同一名获得中医执业医师执照,从事针灸临床工作3年以上的医师使用管针[针管(DONGBANG AcuPrime, Exeter, UK)和银质针灸针(0.30cm×40cm,中研太和公司,北京,中国)]对志愿者进行假针刺刺激右侧外关穴/非穴6分30秒,同时进行假针刺刺激阶段的血氧水平依赖(BOLD)技术的功能性磁共振扫描6分30秒。假针刺：将针头露出套管1mm,采用Block方法设计刺激程序,轻触皮肤,30秒后轻提针柄,使针头离开皮肤表面,30秒后再次压下针柄使针头露出1mm,轻触皮肤,如此反复。检测参数：GR (gradient recalled)/EPI (Echo-Planar imaging)/90, TR3000ms/20ms/FE, Flip angle90, FOV24cm×24cm,层厚6mm/间隔1.0mm,矩阵96×96/NEX=1,Phase Per location:130,2600/6min30s。⑤然后进行3D扫描6分钟2秒后。检测参数：Ax(轴位)3D T1FSPGR (fast spoiled gradient echo)/20T1450, TR7.6ms/TE3.3ms, FOV24cm×18cm, Flip angle20, Bandwidth25,矩阵256×256/NEX=1,thick1.2mm/-0.6mmov,共248层,6min2s。⑥继续对同一批病人再进行真针刺(针具同上文④)刺激右侧外关穴6分30秒,同时进行真针刺刺激阶段的BOLD技术的功能性磁共振扫描6分30秒。真针刺：医师左手挟持针管,右手食指轻敲银质针灸针针柄进针,移开套管,将针再垂直刺入15±2mm,医生感觉手下有沉涩感后,采用平补平泻手法,均匀捻转,捻转幅度±180°,频率60次/min。针刺刺激程序采用Block方法设计：捻转30秒,停止捻针30秒,又重复捻针、不捻针,如此反复。检测参数同上文④。
数据处理：①数据先采用统计参数图(statistical parametric mapping, SPM2)软件包(download from http://www.fil.ion.ac.uk/)在MATLAB6.5(MathWorks公司,美国)平台下进行处理,获取统计参数图。a.预处理：首先对各缺血性脑卒中病人进行头动校正以消除实验中被试者头部的轻微运动；然后把数据进行标准化到MNI空间(the Montreal Neurological Institute space)的标准脑模板(aprocedure of SPM2Software)上；继而进行高斯平滑,减少图像建立过程中产生的误差和消除不同被试者脑结构上的细微差异等。b.初次分析：基于广义线性模型对图像进行逐像素分析,统计分析采用两样本单边t检验,计算出每个像素对应的t值,最后绘制由t值构成的统计参数图,并将有显著性差异(P≤0.001,uncorrected, K>30)的脑区融合到标准结构图像上,即可见被试者在刺激状态下与控制状态下大脑各个脑区对针刺反应的不同,并将这些有变化的脑区叠加到一个由各被试结构像制作而成的平均脑模板上表示出来。获取真针刺/假针刺缺血性脑卒中病人右侧外关穴的统计参数图和激活/负激活的con文件。c.二次分析：选择真针刺/假针刺缺血性脑卒中病人右侧外关穴生成的激活/负激活的con文件,进行真针刺和假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区比较的二次分析,统计采用两独立样本t检验,余同上文b。获取真针刺/假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区差异的统计参数图。②.确定脑区定位和解剖位置。从SPM软件包中制作的上述统计参数图里复制中心坐标,输入软件Talairach Client (download from http://www.talairach.org/client. html),经处理后,得出脑功能区的解剖位置和BA区定位,并请有经验的神经内科医师根据解剖知识和临床经验进行校正。
结果
1.被试者详细资料纳入的24例缺血性脑卒中患者,外关穴组2例和非穴组1例因扫描时患者剧烈运动,中止扫描,数据予以剔除。其中外关穴组病人男性9例,女性1例；年龄47-65岁,平均56.10±5.53岁；病程1-12月,平均5.30±3.71月；CSS评分15-27分,平均18.20±4.02分；9例有高血压病史,2例有糖尿病病史。非穴组病人男性9例,女性2例；年龄48-65岁,平均59.27±6.13岁；病程1-12月,平均4.09±3.83月；CSS评分11-15分,平均16.91±5.24分；9例有高血压病史,2例有糖尿病病史。两组余下志愿者一般资料比较无统计学差异,有可比性。纳入的6例健康志愿者均完成试验,无1例数据剔除。其中,男性3例,女性3例；年龄21-27岁,平均23.33±2.61岁。
2.针刺和假针刺缺血性脑卒中病人外关穴的fMRI脑功能成像比较研究结果
针刺缺血性脑卒中病人右侧外关穴激活/负激活的脑区：左侧脑部Brodmann area(BA)10、18、21和右侧BA7、17、19、23、39、40出现激活点；左侧BA3、6、10、21和右侧BA3、4、5、10出现负激活点。
假针刺缺血性脑卒中病人右侧外关穴激活/负激活的脑区：仅有双侧脑区BA7出现负激活。
真针刺和假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区比较的差异：与假针刺比较,真针刺外关穴后激活相对减弱的脑区有右侧BA2、3、4和6；负激活相对增强的脑区有右侧BA3、4和6。
3.针刺缺血性脑卒中病人外关穴和非穴的fMRI脑功能成像比较研究结果
针刺缺血性脑卒中病人右侧非穴激活/负激活的脑区：右侧脑部BA7出现激活点,左侧脑部BA10出现负激活点。
假针刺缺血性脑卒中病人右侧非穴激活/负激活的脑区：未出现激活点和负激活点。
针刺缺血性脑卒中病人右侧外关穴和非穴激活/负激活脑区比较的差异：与针刺非穴比较,针刺外关穴针刺后仅有激活相对减弱的脑区右侧BA5。
4.针刺缺血性脑卒中病人、健康志愿者外关穴的fMRI脑功能成像比较研究结果
针刺健康志愿者右侧外关穴激活/负激活的脑区：左侧脑部BA6、8、13、18、19、20、21、22、37、40、42、44、47、豆状核下方、壳核、小脑扁桃体后部、屏状核下部和颞下回,及右侧脑部BA6、13、19、20、21、22、27、37、38、40、42、45、垂体下半月小叶、小脑蚓垂后部、丘脑下部、豆状核下方、壳核、颞叶下方、海马回、枕叶和颞下回出现激活点。左侧脑部BAl、3、4、6、18、31、40,及右侧脑部BA1、5、10、11出现负激活点。
针刺外关穴后缺血性脑卒中病人和健康人激活脑区的差异：与健康人比较,病人针刺后激活相对增强的脑区在左右脑均有分布,左侧较为集中分布在BA5、6、7、18、19、24、32,以及丘脑下方；右侧较为集中分布在BA4、6、7、18、19和32。激活相对减弱的脑区主要分布在左侧,较为集中分布在BA13、岛叶下部、小脑扁桃体后部、丘脑下方、乳头体、丘脑下方腹后外侧核和山顶前叶；右侧脑区主要集中在BA13。
针刺外关穴后缺血性脑卒中病人和健康人负激活脑区的差异：与健康人比较,病人针刺后负激活相对增强的脑区在左右脑均有分布,左侧较为集中分布在BA6、11、20、22、37、47,以及小脑舌前部、小脑扁桃体后部和小脑山顶前部；右侧较为集中分布在BA8、37、45、47,以及小脑山顶前部、小脑结节前部、豆状核叶下方、外侧苍白球、颞叶下方和海马回。负激活相对减弱的脑区为左侧脑区BA7。
结论
本研究通过比较初步表明外关穴针刺和假针刺、外关穴和非穴、正常人和缺血性脑卒中病人外关穴针刺之间均存在着一定差异；同时研究初步表明针刺外关穴特异性的指向性激活／负激活,可能是外关穴治疗缺血性脑卒中运动障碍、感觉障碍、视觉障碍和失语的机制之一,也初步佐证了针刺外关穴中枢调控是基于网络调控来实现的。
Objective
In this study, we observed the active/negative encephalic region activation specialty effects of needling Waiguan (TE5) in ischemic stroke patients by functional brain imaging techniques. And observed the fMRI cerebral function imaging comparison of Waiguan (TE5) sham needling, non-acupoint needling and Waiguan (TE5) needling on normal people, analysis the relative specificity of Waiguan (TE5) acupuncture on ischemic stroke patients from different angles, to provide a preliminary basis for the elaborate mechanism of acupuncture treatment for stroke.
Methods
1. Design
A block design; Neuroimaging study.
2. Time and setting
The experiment was performed at the MRI Center, Nanfang Hospital, China, from October2008to August2010.
3. Ethics Committee
The study program was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine [(2008)024], and registered in Chinese clinical trials online(http://www.chictr.org), registration ID:ChiCTR-NRC-00000255.
4. Volunteers
24cases of ischemic stroke patients are from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and divided into TE5group and non-acupoint group (n=12) randomly by random number table.6healthy volunteers are from the Southern Medical University. Each volunteer signed an informed consent before the test.
5. Ischemic stroke diagnostic criteria
The Traditional Chinese Medicine (TCM) diagnosis standards in line with apoplexy standard of stroke diagnosis and therapeutic evaluation diagnosis, which published in the journal of Beijing University of Traditional Chinese Medicine by State Administration of Traditional Chinese Medicine encephalopathy acute Collaborative Group,1996"(Gen2). Western diagnostic criteria in line with the article diagnostic criteria of various types of brain disease diagnostic points in ischemic stroke from the Neuroscience Society and the Neurosurgery society in the Fourth National Cerebrovascular Disease Conference,1995.
6. Inclusion criteria
①Ischemic stroke inclusion criteria:a. Patients were coincident the diagnostic criteria above and suffered with left basal ganglion ischemia proved, which manifested as the typical hemiplagia of right side (Upper limbs and/or lower extremity muscle strength stroke clinical neurological function deficit scores Scale score≥4points) and sensory disturbance; b. Patients passed the acute state and were under the stable pathogenic condition; c. Patients ate and slept almost regularly, did not over smoke and over drink tea or coffee, and were not over weighted (18.5≤BMI≤23.9); d. Patients just received the basic treatment and the therapy had not been changed during the last month before the experiment; e. The ages of the patients were40-65years old; f. Patients were right handedness.
②Healthy volunteers inclusion criteria:a. Aged between21-28years old, male or female college students; b. volunteers ate and slept almost regularly, did not over smoke and over drink tea or coffee, and were not over weighted (18.5≤BMI≤23.9); c. volunteers haven't received acupuncture treatment within a month; d. No metal in the body (such as cardiac stents); e. Volunteers were right handedness; f. No history of mental illness such as claustrophobia; g. No acupuncture contraindications such as hemophilia.
7. Exterior criteria
①Ischemic stroke exerior criteria:a. Patient whose disease history was more than1year; b. Patient who received acupuncture treatment4weeks before the experiment; c. Patient combined serious diseases, such as serious dysfunction of heart, liver and kidney, serious infection, malignant hypertension and malignant tumor, etc; d. Patients suffered from serious aphasia, unconsciousness and mental disorders (including Fear of confined spaces), which affected the cooperation during the experiment; e. Pregnant or lactation woman; f. Patient with some metal being set in his/her body, such as cardiac supporter, cardiac pacemaker and metal pontic; g. Patient suffered from thrombocytopenia or hemophilia, which belong to the counterindication of acupuncture;②Healthy volunteers exterior criteria:a. Volunteers who can not cooperate with the experimental (who refused to sign an informed consent or unreasonably withheld the study, etc.); b. At physiological period (female).
8. Study Procedures
①Subjects (ischemic stroke patients or healthy subjects) were conventional closed vision and auditory till the end of the fMRI detects(Earplugs from Aearo Company, USA, batch R5A018; goggles from Hanjiang Jiang Xinhua Tourist Products Factory, Yangzhou, China, batch XHYZ-001).
②Ischemic stroke patients received the TE5and non-acupuncture stimulation randomly, healthy volunteers only to accept TE5acupuncture stimulation, the same subjects received sham acupuncture and real acupuncture in succession. TE5locates on the forearm,2cun (cun, a special length unit in acupuncture. The distance between the transverse crease of the elbow and that of the wrist is12cun.) above the transverse crease of the dorsum of wrist, between the radius and ulna. Location of the sham acupoint:Level with TE5, on the midpoint of the lines in forearm where Sanjiao Meridian of hand-Shaoyang and Small intestine meridian of hand-Taiyang travel.
③fMRI scanning was performed with a3.0T whole-body MRI scanner (GE, Bethesda, MD, USA) and a standard head coil. The subjects used earplugs (Aearo Co., Hartford, CT, USA) and were blindfolded (Xinhua Tourism Co., Hangzhou, China). Each subject rested on the bed for5-10minutes before the scan.3D anatomy images were collected with a T1-weighted3D gradient echo-pulse fast spin sequence prior to acupuncture, with axial view T1fluid-attenuated-inversion-recovery scan (repetition time,2300ms; echo time,21ms; time of inversion,920ms; slice thickness,6.0mm; gap1.0mm for20layers for a total of2minutes45seconds; field of view,24cm×18cm; matrix,320×256; number of excitations=2; field of view echo train length,9; and band width,50).
④Acupuncture was performed by one physician, who had engaged in clinical acupuncture for more than three years. The tubes were purchased from Dongbang AcuPrime Co.(Exeter, England) and the0.3cm×40cm silver needles from Zhongyan Taihe Co.(Beijing, China). Volunteers received sham acupuncture stimulation on right TE5/non-point6minutes and30seconds, at the same time scanned sham acupuncture stimulation stage blood oxygen level dependent (BOLD) functional magnetic resonance6minutes and30seconds. Sham needling:the location of TE5, the sterilization, the needling instruments were the same as above. The stimulation was designed with the block procedure of the alternative of gently touching the skin with the tip of the needle lmm above the tube for30seconds or non-touching the skin with lifting the needle for each30seconds, and the stimulation was lasted to360seconds totally, too. Detection parameters:The GR (gradient the recalled)/EPI (Echo-Planar imaging)/90, TR3000ms/20ms/FE Flip angle90, FOV24cm x24cm, thickness6mm/interval1.0mm, matrix96×96/NEX=1, PhasePer location:130,2600/6min30s.
⑤And3D scanning after6minutes2seconds. Detection parameters:Ax (axial) of3D T1FSPGR (fast spoiled gradient echo)/20T1450, TR7.6ms/TE 3.3ms, FOV24cm x18cm, Flip angle20Bandwidth25, matrix256×256/NEX=1, thick1.2mm/-0.6mmov, a total of248layers,6min2s.
⑥Continue true acupuncture (needles instrument the same as④) to stimulate the right TE5on the same group of patients6minutes and30seconds, the true acupuncture stimulation stage BOLD functional MRI scans of6minutes and30seconds. True needling:sterilized the local skin routinely and inserted the needle with tube insertion method (the tubes were from DONGBANG AcuPrime Co., England and the silver needles of0.3×40cm were from Zhongyan Taihe Co., China). The physician sticked the auxiliary part of the tube on the local skin, put the needle into the matching tube over the acupoint and tapped the end of the needle to make the tip of the needle inserted, removed away the tube and punctured the needle to the depth of15±2mm, and twirled the handle of the needle to get the needling sensation. Then the physician manually stimulated the needle with an even reinforcing and reducing manipulation by twirling the needling with±180°nd60times/min. The stimulation was designed with the block procedure of the alternative of twirling or non-twirling for each30seconds, and the stimulation was lasted to360seconds totally. Detection parameters the same with④.
9. Study Procedures
①The fMRI data were processed with the software SPM2(http://www.fil.ion.ac.uk) MATLAB6.5(The MathWorks, Inc., USA) platform for processing to obtain statistical parameters Figure. a. Pre-Processing:Slight movements of the head were corrected; The images were normalized to the standard brain template of the Montreal Neurological Institute space; and then smoothed spatially to reduce errors produced during imaging construction and eliminate tiny differences in brain structures among subjects; b. First analysis:The smoothed data were analyzed with a generalized linear model voxel by voxel. The value of each voxel was calculated by two-sample t-tests, and statistical parametric mapping was based on the t values (P<0.001, uncorrected, K>30). Significant changes in different brain regions during stimulation and control conditions were identified and superimposed on the standard brain image mode of each subject's anatomic images; c. Secondary Analysis:the activated/deactivated con file of the model of stroke patients and normal controls was further analyzed using a two-independent sample t-test. The remaining procedures were the same as those reported in.
②Determine the brain area location and anatomical position:Central coordinates from statistical parameters determined using SPM software package were reproduced and input in Talairach Client (download from http://www.talairach.org/client.html) to obtain the anatomical location and the BA range of the functional areas of the brain, which were corrected by a physician of the neurological medicine department according to anatomic knowledge and clinical experience.
Results
1. Subjects
The subjects include details of24cases of patients with ischemic stroke, scanning of2patients of TE5group and1case of non-acupoint group was broke off for strenuous movements, and the data was removed. There were9male patients and1female in TE5group; aged47-65years old, with an average of56.10±5.53years; course of disease from1month to12months, an average of5.30±3.71months; CSS score15-27points, an average of18.20±4.02points;9patients had a history of hypertension, a history of diabetes in the two cases. Patients with non-acupoint group including9male and2female; ages48-65years old, with an average of59.27±6.13years; course of disease from1month to12months, an average of4.09±3.83months; CSS score11-15points, with an average of16.91±5.24;9patients with a history of hypertension,2patients had a history of diabetes. General information of the remaining volunteers in the two groups have no significant difference between comparable.6cases included healthy volunteers completed the trial, no data removed.3males and3females; ages21-27years old, an average of23.33±2.61years old.
2. The fMRI brain function imaging comparative study results of true acupuncture and sham acupuncture ischemic stroke patients on TE5.
The true needling of TE5activated the areas of BA7,10,17,18,19,21, 23,39,40, while BA3,4,5,6,10,21were deactivated. The activated areas in the right cerebral regions are more than those in the left. The number of the deactivated areas is the same in the both sides.
No activated area was elicited in the sham needling of TE5. BA7of both cerebral regions were deactivated.
Compared with the activated area by true needling, sham needling significantly activated BA2,3,4and6. True needling significantly deactivated BA3,4, and6with a comparison of the areas deactivated by sham needling.
3. The fMRI brain function imaging comparative study results of TE5acupuncture and non-acupoint acupuncture on ischemic stroke patients.
Acupuncture the right non-acupoints active/deactivation of brain regions of ischemic stroke patients:the right side of the brain the B A7appear activated point, the left brain BA10appear deactivation point.
Sham acupuncture the right non-acupoints activation/deactivated brain regions in patients with ischemic stroke:no activation point and deactivation point appear.
Difference of acupuncture the right TE5and non-acupoint activation/deactivation brain regions in patients with ischemic stroke:compared with that of acupuncture non-acupoints, acupuncture the TE5can only activate relatively weakened right side brain regions BA5.
4. Differences in fMRI brain function imaging between acupuncture at TE5on stroke patients and healthy controls.
Acupuncture the right TE5active/deactivation brain regions of healthy controls:The left side of the brain BA6,8,13,18,19,20,21,22,37,40,42,44,47, below the lenticular nucleus, putamen, cerebellum tonsil rear, lower part of the claustrum and infratemporalback, and the right side of the brain BA613,19,20,21,22,27,37,38,40,42,45pituitary second half of lobular cerebellar vermis vertical rear hypothalamus, below the lenticular nucleus,putamen, the bottom of the temporal lobe, hippocampal gyrus, occipital lobe and inferior temporal gyrus appear activation point. The left brain BA1,3,4,6,18,31,40, and the right side of the brain the BA1,5,10,11appear deactivation point.
Differences in activated brain areas between stroke patients and healthy controls after acupuncture at TE5:Compared with healthy controls, patients with relatively enhanced activate brain regions in the right side of the left and right brain after acupuncture, the left is more concentrated in BA5,6,7,18,19,24,32, as well as the hypothalamus the bottom; more concentrated distribution in BA4,6,7,18,19and32. Activated relatively weakened areas of the brain are mainly distributed in the left, more concentrated in BA13, the lower part of the insular lobe, the back of tonsil of cerebellum, below the thalamus, corpus albicans, hypothalamus below the anterior lobe of the ventral posterior lateral nucleus and the peak anterior lobe; mainly focused on regions BA13of right brain.
Differences in deactivated brain areas between stroke patients and healthy controls after acupuncture at TE5:Compared with healthy controls, the relative enhancement of patient deactivation brain regions are distributed in the left and right brain after acupuncture, the left is more concentrated in BA6,11,20,22,37,47, and front lingula of cerebellum, the back of the cerebellar tonsils and the peak anterior lobe of cerebellum; right side is more concentrated in BA8,37,45,47, as well as the peak anterior lobe of cerebellum, the front of the cerebellum nodules, below the lenticular nucleus leaves, outside of the globus pallidus, the bottom of the temporal lobe and hippocampal gyrus. Deactivate brain regions relative weakening of the left brain area BA7.
Conclusion
By comparing This study preliminary indicated there are some differences among the acupuncture TE5and sham acupuncture, acupuncture TE5and non-acupoints, acupuncture TE5between normal subjects and patients with ischemic stroke; At the same time, the study shows that acupuncture TE5specificity directional activation/deactivations, it may be one of the mechanisms of TE5treatment of ischemic stroke movement disorders, sensory impairments, visual impairments and the aphasia, also preliminary corroborated central regulation of acupuncture TE5is to implement network-based regulation.
本研究运用脑功能成像技术,观察针刺缺血性脑卒中病人外关穴对脑区的激活/负激活的特点,并观察比较其与缺血性脑卒中病人外关穴假针刺和非穴针刺、正常人外关穴针刺fMRI脑功能成像特点的差异,从不同角度来分析针刺缺血性脑卒中病人外关穴的相对特异性,为阐述针刺治疗中风的机理提供初步依据。
方法
设计：组块设计(Block设计),神经影像学研究。
时间和地点：实验于2008年10月至2010年8月在南方医院MRI影像中心完成。
伦理批注：试验方案获得广州中医药大学第一附属医院伦理委员会批准[(2008)024],并在中国临床试验网上注册(http://www.chictr.org),注册号(ChiCTR-NRC-00000255)。
被试者来源：24例缺血性脑卒中病人均来自广州中医药大学第一附属医院,通过随机数字表法,随机分为外关穴组和非穴组,每组12人。6名健康志愿者均来自南方医科大学。试验前各志愿者均签署知情同意书。
缺血性脑卒中诊断标准：中医诊断标准符合1996年国家中医药管理局脑病急症协作组刊于《北京中医药大学学报》的《中风病诊断与疗效评定诊断》(二代标准)中中风病相关标准。西医诊断标准符合中华神经科学会、中华神经外科学会于1995年在第四届全国脑血管病学术会议制订的《各类脑血管病诊断要点》中缺血性脑卒中的诊断标准。
纳入标准：①缺血性脑卒中纳入标准：a.符合上述诊断标准,且病灶以左侧基底节区为主的缺血性脑卒中患者,有典型的右侧偏身运动(上肢肌力和/或下肢肌力脑卒中临床神经功能缺损程度评分量表评分≥4分)和感觉障碍者；b.度过急性期,病情稳定者；c.饮食规律,不嗜烟、酒、茶、咖啡,睡眠正常,体型适中[18.5≤体质指数(BMI)≤23.9]；d.接受西医基础治疗(拜阿司匹林/波立维等抗血小板聚集、立普妥/舒降之等降脂稳定斑块、凯时/舒血宁/碟脉灵/凯那等改善循环等),治疗方案在试验前1个月没有改变者；e.年龄在40周岁以上,65周岁以下；f右利手。②健康志愿者纳入标准：a.年龄在21-28岁之间在校大学生,男女不限；b.平素身体健康,饮食规律,不嗜烟、酒、茶、咖啡,睡眠正常,体型适中[18.5≤体质指数(BMI)≤23.9]；c.近1个月内未接受过针刺治疗；d.体内无金属类物质(如心脏支架)；e.右利手；f无幽闭恐怖症等精神病史；g.无血友病等针刺禁忌证。
排除标准：①缺血性脑卒中排除标准：a.病程长于1年者；b.试验前1个月内接受过针刺治疗者；c.有严重心、肝、肾疾病及肿瘤者；d.严重失语,或有痴呆、幽闭恐怖症等精神病史,影响实验过程中的交流和操作者；e.妊娠、哺乳期妇女；f体内有金属类物质(如心脏支架)者；g.患有血友病等针刺禁忌证者。②健康志愿者排除标准：a.不能配合实验(如拒绝签订知情同意书及无故拒绝试验等)者；b.处于生理期内(女)。
试验过程：①各被试者(缺血性脑卒中病人或正常人)常规封闭视听至fMRI检测结束(耳塞产自美国Aearo公司,批号R5A018,眼罩产自扬州市邗江鑫华旅游用品厂,批号XHYZ-001)。②缺血性脑卒中病人随机接受外关穴和非穴针刺刺激,健康志愿者只接受外关穴针刺刺激,同一被试者先后接受假针刺和真针刺。外关穴定位：在前臂背侧,当阳池与肘尖的连线上,腕背横纹上2寸(平肘尖的肘横纹和腕掌侧横纹之间的距离为12寸),尺骨与桡骨之间处。非穴定位：与外关穴相平,手少阳三焦经与少太阳小肠经在前臂循行线上连线的中点。③被试者在检查床上休息5分钟后,采用美国GE公司生产的3.0T超导MRI系统和及其标准头部线圈,首先进行T1W1三维梯度回波脉冲序列采集MR解剖图像,扫描2分42秒。检测序列为：OAX(轴位)T1FLAIR (Fluid attenuated inversion recovery),重复时间(TR)2300ms/回波时间(TE)21ms,TI(time of inversion)920ms,层厚6.0mm/间隔1.0mm；共20层,2min45s,视野(FOV)240mm×180mm/Z,矩阵320×256/NEX (number of excitations)=2, Matrix=320×256,回波链长度=9,带宽=50。④接着由同一名获得中医执业医师执照,从事针灸临床工作3年以上的医师使用管针[针管(DONGBANG AcuPrime, Exeter, UK)和银质针灸针(0.30cm×40cm,中研太和公司,北京,中国)]对志愿者进行假针刺刺激右侧外关穴/非穴6分30秒,同时进行假针刺刺激阶段的血氧水平依赖(BOLD)技术的功能性磁共振扫描6分30秒。假针刺：将针头露出套管1mm,采用Block方法设计刺激程序,轻触皮肤,30秒后轻提针柄,使针头离开皮肤表面,30秒后再次压下针柄使针头露出1mm,轻触皮肤,如此反复。检测参数：GR (gradient recalled)/EPI (Echo-Planar imaging)/90, TR3000ms/20ms/FE, Flip angle90, FOV24cm×24cm,层厚6mm/间隔1.0mm,矩阵96×96/NEX=1,Phase Per location:130,2600/6min30s。⑤然后进行3D扫描6分钟2秒后。检测参数：Ax(轴位)3D T1FSPGR (fast spoiled gradient echo)/20T1450, TR7.6ms/TE3.3ms, FOV24cm×18cm, Flip angle20, Bandwidth25,矩阵256×256/NEX=1,thick1.2mm/-0.6mmov,共248层,6min2s。⑥继续对同一批病人再进行真针刺(针具同上文④)刺激右侧外关穴6分30秒,同时进行真针刺刺激阶段的BOLD技术的功能性磁共振扫描6分30秒。真针刺：医师左手挟持针管,右手食指轻敲银质针灸针针柄进针,移开套管,将针再垂直刺入15±2mm,医生感觉手下有沉涩感后,采用平补平泻手法,均匀捻转,捻转幅度±180°,频率60次/min。针刺刺激程序采用Block方法设计：捻转30秒,停止捻针30秒,又重复捻针、不捻针,如此反复。检测参数同上文④。
数据处理：①数据先采用统计参数图(statistical parametric mapping, SPM2)软件包(download from http://www.fil.ion.ac.uk/)在MATLAB6.5(MathWorks公司,美国)平台下进行处理,获取统计参数图。a.预处理：首先对各缺血性脑卒中病人进行头动校正以消除实验中被试者头部的轻微运动；然后把数据进行标准化到MNI空间(the Montreal Neurological Institute space)的标准脑模板(aprocedure of SPM2Software)上；继而进行高斯平滑,减少图像建立过程中产生的误差和消除不同被试者脑结构上的细微差异等。b.初次分析：基于广义线性模型对图像进行逐像素分析,统计分析采用两样本单边t检验,计算出每个像素对应的t值,最后绘制由t值构成的统计参数图,并将有显著性差异(P≤0.001,uncorrected, K>30)的脑区融合到标准结构图像上,即可见被试者在刺激状态下与控制状态下大脑各个脑区对针刺反应的不同,并将这些有变化的脑区叠加到一个由各被试结构像制作而成的平均脑模板上表示出来。获取真针刺/假针刺缺血性脑卒中病人右侧外关穴的统计参数图和激活/负激活的con文件。c.二次分析：选择真针刺/假针刺缺血性脑卒中病人右侧外关穴生成的激活/负激活的con文件,进行真针刺和假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区比较的二次分析,统计采用两独立样本t检验,余同上文b。获取真针刺/假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区差异的统计参数图。②.确定脑区定位和解剖位置。从SPM软件包中制作的上述统计参数图里复制中心坐标,输入软件Talairach Client (download from http://www.talairach.org/client. html),经处理后,得出脑功能区的解剖位置和BA区定位,并请有经验的神经内科医师根据解剖知识和临床经验进行校正。
结果
1.被试者详细资料纳入的24例缺血性脑卒中患者,外关穴组2例和非穴组1例因扫描时患者剧烈运动,中止扫描,数据予以剔除。其中外关穴组病人男性9例,女性1例；年龄47-65岁,平均56.10±5.53岁；病程1-12月,平均5.30±3.71月；CSS评分15-27分,平均18.20±4.02分；9例有高血压病史,2例有糖尿病病史。非穴组病人男性9例,女性2例；年龄48-65岁,平均59.27±6.13岁；病程1-12月,平均4.09±3.83月；CSS评分11-15分,平均16.91±5.24分；9例有高血压病史,2例有糖尿病病史。两组余下志愿者一般资料比较无统计学差异,有可比性。纳入的6例健康志愿者均完成试验,无1例数据剔除。其中,男性3例,女性3例；年龄21-27岁,平均23.33±2.61岁。
2.针刺和假针刺缺血性脑卒中病人外关穴的fMRI脑功能成像比较研究结果
针刺缺血性脑卒中病人右侧外关穴激活/负激活的脑区：左侧脑部Brodmann area(BA)10、18、21和右侧BA7、17、19、23、39、40出现激活点；左侧BA3、6、10、21和右侧BA3、4、5、10出现负激活点。
假针刺缺血性脑卒中病人右侧外关穴激活/负激活的脑区：仅有双侧脑区BA7出现负激活。
真针刺和假针刺缺血性脑卒中病人右侧外关穴激活/负激活脑区比较的差异：与假针刺比较,真针刺外关穴后激活相对减弱的脑区有右侧BA2、3、4和6；负激活相对增强的脑区有右侧BA3、4和6。
3.针刺缺血性脑卒中病人外关穴和非穴的fMRI脑功能成像比较研究结果
针刺缺血性脑卒中病人右侧非穴激活/负激活的脑区：右侧脑部BA7出现激活点,左侧脑部BA10出现负激活点。
假针刺缺血性脑卒中病人右侧非穴激活/负激活的脑区：未出现激活点和负激活点。
针刺缺血性脑卒中病人右侧外关穴和非穴激活/负激活脑区比较的差异：与针刺非穴比较,针刺外关穴针刺后仅有激活相对减弱的脑区右侧BA5。
4.针刺缺血性脑卒中病人、健康志愿者外关穴的fMRI脑功能成像比较研究结果
针刺健康志愿者右侧外关穴激活/负激活的脑区：左侧脑部BA6、8、13、18、19、20、21、22、37、40、42、44、47、豆状核下方、壳核、小脑扁桃体后部、屏状核下部和颞下回,及右侧脑部BA6、13、19、20、21、22、27、37、38、40、42、45、垂体下半月小叶、小脑蚓垂后部、丘脑下部、豆状核下方、壳核、颞叶下方、海马回、枕叶和颞下回出现激活点。左侧脑部BAl、3、4、6、18、31、40,及右侧脑部BA1、5、10、11出现负激活点。
针刺外关穴后缺血性脑卒中病人和健康人激活脑区的差异：与健康人比较,病人针刺后激活相对增强的脑区在左右脑均有分布,左侧较为集中分布在BA5、6、7、18、19、24、32,以及丘脑下方；右侧较为集中分布在BA4、6、7、18、19和32。激活相对减弱的脑区主要分布在左侧,较为集中分布在BA13、岛叶下部、小脑扁桃体后部、丘脑下方、乳头体、丘脑下方腹后外侧核和山顶前叶；右侧脑区主要集中在BA13。
针刺外关穴后缺血性脑卒中病人和健康人负激活脑区的差异：与健康人比较,病人针刺后负激活相对增强的脑区在左右脑均有分布,左侧较为集中分布在BA6、11、20、22、37、47,以及小脑舌前部、小脑扁桃体后部和小脑山顶前部；右侧较为集中分布在BA8、37、45、47,以及小脑山顶前部、小脑结节前部、豆状核叶下方、外侧苍白球、颞叶下方和海马回。负激活相对减弱的脑区为左侧脑区BA7。
结论
本研究通过比较初步表明外关穴针刺和假针刺、外关穴和非穴、正常人和缺血性脑卒中病人外关穴针刺之间均存在着一定差异；同时研究初步表明针刺外关穴特异性的指向性激活／负激活,可能是外关穴治疗缺血性脑卒中运动障碍、感觉障碍、视觉障碍和失语的机制之一,也初步佐证了针刺外关穴中枢调控是基于网络调控来实现的。
Objective
In this study, we observed the active/negative encephalic region activation specialty effects of needling Waiguan (TE5) in ischemic stroke patients by functional brain imaging techniques. And observed the fMRI cerebral function imaging comparison of Waiguan (TE5) sham needling, non-acupoint needling and Waiguan (TE5) needling on normal people, analysis the relative specificity of Waiguan (TE5) acupuncture on ischemic stroke patients from different angles, to provide a preliminary basis for the elaborate mechanism of acupuncture treatment for stroke.
Methods
1. Design
A block design; Neuroimaging study.
2. Time and setting
The experiment was performed at the MRI Center, Nanfang Hospital, China, from October2008to August2010.
3. Ethics Committee
The study program was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine [(2008)024], and registered in Chinese clinical trials online(http://www.chictr.org), registration ID:ChiCTR-NRC-00000255.
4. Volunteers
24cases of ischemic stroke patients are from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and divided into TE5group and non-acupoint group (n=12) randomly by random number table.6healthy volunteers are from the Southern Medical University. Each volunteer signed an informed consent before the test.
5. Ischemic stroke diagnostic criteria
The Traditional Chinese Medicine (TCM) diagnosis standards in line with apoplexy standard of stroke diagnosis and therapeutic evaluation diagnosis, which published in the journal of Beijing University of Traditional Chinese Medicine by State Administration of Traditional Chinese Medicine encephalopathy acute Collaborative Group,1996"(Gen2). Western diagnostic criteria in line with the article diagnostic criteria of various types of brain disease diagnostic points in ischemic stroke from the Neuroscience Society and the Neurosurgery society in the Fourth National Cerebrovascular Disease Conference,1995.
6. Inclusion criteria
①Ischemic stroke inclusion criteria:a. Patients were coincident the diagnostic criteria above and suffered with left basal ganglion ischemia proved, which manifested as the typical hemiplagia of right side (Upper limbs and/or lower extremity muscle strength stroke clinical neurological function deficit scores Scale score≥4points) and sensory disturbance; b. Patients passed the acute state and were under the stable pathogenic condition; c. Patients ate and slept almost regularly, did not over smoke and over drink tea or coffee, and were not over weighted (18.5≤BMI≤23.9); d. Patients just received the basic treatment and the therapy had not been changed during the last month before the experiment; e. The ages of the patients were40-65years old; f. Patients were right handedness.
②Healthy volunteers inclusion criteria:a. Aged between21-28years old, male or female college students; b. volunteers ate and slept almost regularly, did not over smoke and over drink tea or coffee, and were not over weighted (18.5≤BMI≤23.9); c. volunteers haven't received acupuncture treatment within a month; d. No metal in the body (such as cardiac stents); e. Volunteers were right handedness; f. No history of mental illness such as claustrophobia; g. No acupuncture contraindications such as hemophilia.
7. Exterior criteria
①Ischemic stroke exerior criteria:a. Patient whose disease history was more than1year; b. Patient who received acupuncture treatment4weeks before the experiment; c. Patient combined serious diseases, such as serious dysfunction of heart, liver and kidney, serious infection, malignant hypertension and malignant tumor, etc; d. Patients suffered from serious aphasia, unconsciousness and mental disorders (including Fear of confined spaces), which affected the cooperation during the experiment; e. Pregnant or lactation woman; f. Patient with some metal being set in his/her body, such as cardiac supporter, cardiac pacemaker and metal pontic; g. Patient suffered from thrombocytopenia or hemophilia, which belong to the counterindication of acupuncture;②Healthy volunteers exterior criteria:a. Volunteers who can not cooperate with the experimental (who refused to sign an informed consent or unreasonably withheld the study, etc.); b. At physiological period (female).
8. Study Procedures
①Subjects (ischemic stroke patients or healthy subjects) were conventional closed vision and auditory till the end of the fMRI detects(Earplugs from Aearo Company, USA, batch R5A018; goggles from Hanjiang Jiang Xinhua Tourist Products Factory, Yangzhou, China, batch XHYZ-001).
②Ischemic stroke patients received the TE5and non-acupuncture stimulation randomly, healthy volunteers only to accept TE5acupuncture stimulation, the same subjects received sham acupuncture and real acupuncture in succession. TE5locates on the forearm,2cun (cun, a special length unit in acupuncture. The distance between the transverse crease of the elbow and that of the wrist is12cun.) above the transverse crease of the dorsum of wrist, between the radius and ulna. Location of the sham acupoint:Level with TE5, on the midpoint of the lines in forearm where Sanjiao Meridian of hand-Shaoyang and Small intestine meridian of hand-Taiyang travel.
③fMRI scanning was performed with a3.0T whole-body MRI scanner (GE, Bethesda, MD, USA) and a standard head coil. The subjects used earplugs (Aearo Co., Hartford, CT, USA) and were blindfolded (Xinhua Tourism Co., Hangzhou, China). Each subject rested on the bed for5-10minutes before the scan.3D anatomy images were collected with a T1-weighted3D gradient echo-pulse fast spin sequence prior to acupuncture, with axial view T1fluid-attenuated-inversion-recovery scan (repetition time,2300ms; echo time,21ms; time of inversion,920ms; slice thickness,6.0mm; gap1.0mm for20layers for a total of2minutes45seconds; field of view,24cm×18cm; matrix,320×256; number of excitations=2; field of view echo train length,9; and band width,50).
④Acupuncture was performed by one physician, who had engaged in clinical acupuncture for more than three years. The tubes were purchased from Dongbang AcuPrime Co.(Exeter, England) and the0.3cm×40cm silver needles from Zhongyan Taihe Co.(Beijing, China). Volunteers received sham acupuncture stimulation on right TE5/non-point6minutes and30seconds, at the same time scanned sham acupuncture stimulation stage blood oxygen level dependent (BOLD) functional magnetic resonance6minutes and30seconds. Sham needling:the location of TE5, the sterilization, the needling instruments were the same as above. The stimulation was designed with the block procedure of the alternative of gently touching the skin with the tip of the needle lmm above the tube for30seconds or non-touching the skin with lifting the needle for each30seconds, and the stimulation was lasted to360seconds totally, too. Detection parameters:The GR (gradient the recalled)/EPI (Echo-Planar imaging)/90, TR3000ms/20ms/FE Flip angle90, FOV24cm x24cm, thickness6mm/interval1.0mm, matrix96×96/NEX=1, PhasePer location:130,2600/6min30s.
⑤And3D scanning after6minutes2seconds. Detection parameters:Ax (axial) of3D T1FSPGR (fast spoiled gradient echo)/20T1450, TR7.6ms/TE 3.3ms, FOV24cm x18cm, Flip angle20Bandwidth25, matrix256×256/NEX=1, thick1.2mm/-0.6mmov, a total of248layers,6min2s.
⑥Continue true acupuncture (needles instrument the same as④) to stimulate the right TE5on the same group of patients6minutes and30seconds, the true acupuncture stimulation stage BOLD functional MRI scans of6minutes and30seconds. True needling:sterilized the local skin routinely and inserted the needle with tube insertion method (the tubes were from DONGBANG AcuPrime Co., England and the silver needles of0.3×40cm were from Zhongyan Taihe Co., China). The physician sticked the auxiliary part of the tube on the local skin, put the needle into the matching tube over the acupoint and tapped the end of the needle to make the tip of the needle inserted, removed away the tube and punctured the needle to the depth of15±2mm, and twirled the handle of the needle to get the needling sensation. Then the physician manually stimulated the needle with an even reinforcing and reducing manipulation by twirling the needling with±180°nd60times/min. The stimulation was designed with the block procedure of the alternative of twirling or non-twirling for each30seconds, and the stimulation was lasted to360seconds totally. Detection parameters the same with④.
9. Study Procedures
①The fMRI data were processed with the software SPM2(http://www.fil.ion.ac.uk) MATLAB6.5(The MathWorks, Inc., USA) platform for processing to obtain statistical parameters Figure. a. Pre-Processing:Slight movements of the head were corrected; The images were normalized to the standard brain template of the Montreal Neurological Institute space; and then smoothed spatially to reduce errors produced during imaging construction and eliminate tiny differences in brain structures among subjects; b. First analysis:The smoothed data were analyzed with a generalized linear model voxel by voxel. The value of each voxel was calculated by two-sample t-tests, and statistical parametric mapping was based on the t values (P<0.001, uncorrected, K>30). Significant changes in different brain regions during stimulation and control conditions were identified and superimposed on the standard brain image mode of each subject's anatomic images; c. Secondary Analysis:the activated/deactivated con file of the model of stroke patients and normal controls was further analyzed using a two-independent sample t-test. The remaining procedures were the same as those reported in.
②Determine the brain area location and anatomical position:Central coordinates from statistical parameters determined using SPM software package were reproduced and input in Talairach Client (download from http://www.talairach.org/client.html) to obtain the anatomical location and the BA range of the functional areas of the brain, which were corrected by a physician of the neurological medicine department according to anatomic knowledge and clinical experience.
Results
1. Subjects
The subjects include details of24cases of patients with ischemic stroke, scanning of2patients of TE5group and1case of non-acupoint group was broke off for strenuous movements, and the data was removed. There were9male patients and1female in TE5group; aged47-65years old, with an average of56.10±5.53years; course of disease from1month to12months, an average of5.30±3.71months; CSS score15-27points, an average of18.20±4.02points;9patients had a history of hypertension, a history of diabetes in the two cases. Patients with non-acupoint group including9male and2female; ages48-65years old, with an average of59.27±6.13years; course of disease from1month to12months, an average of4.09±3.83months; CSS score11-15points, with an average of16.91±5.24;9patients with a history of hypertension,2patients had a history of diabetes. General information of the remaining volunteers in the two groups have no significant difference between comparable.6cases included healthy volunteers completed the trial, no data removed.3males and3females; ages21-27years old, an average of23.33±2.61years old.
2. The fMRI brain function imaging comparative study results of true acupuncture and sham acupuncture ischemic stroke patients on TE5.
The true needling of TE5activated the areas of BA7,10,17,18,19,21, 23,39,40, while BA3,4,5,6,10,21were deactivated. The activated areas in the right cerebral regions are more than those in the left. The number of the deactivated areas is the same in the both sides.
No activated area was elicited in the sham needling of TE5. BA7of both cerebral regions were deactivated.
Compared with the activated area by true needling, sham needling significantly activated BA2,3,4and6. True needling significantly deactivated BA3,4, and6with a comparison of the areas deactivated by sham needling.
3. The fMRI brain function imaging comparative study results of TE5acupuncture and non-acupoint acupuncture on ischemic stroke patients.
Acupuncture the right non-acupoints active/deactivation of brain regions of ischemic stroke patients:the right side of the brain the B A7appear activated point, the left brain BA10appear deactivation point.
Sham acupuncture the right non-acupoints activation/deactivated brain regions in patients with ischemic stroke:no activation point and deactivation point appear.
Difference of acupuncture the right TE5and non-acupoint activation/deactivation brain regions in patients with ischemic stroke:compared with that of acupuncture non-acupoints, acupuncture the TE5can only activate relatively weakened right side brain regions BA5.
4. Differences in fMRI brain function imaging between acupuncture at TE5on stroke patients and healthy controls.
Acupuncture the right TE5active/deactivation brain regions of healthy controls:The left side of the brain BA6,8,13,18,19,20,21,22,37,40,42,44,47, below the lenticular nucleus, putamen, cerebellum tonsil rear, lower part of the claustrum and infratemporalback, and the right side of the brain BA613,19,20,21,22,27,37,38,40,42,45pituitary second half of lobular cerebellar vermis vertical rear hypothalamus, below the lenticular nucleus,putamen, the bottom of the temporal lobe, hippocampal gyrus, occipital lobe and inferior temporal gyrus appear activation point. The left brain BA1,3,4,6,18,31,40, and the right side of the brain the BA1,5,10,11appear deactivation point.
Differences in activated brain areas between stroke patients and healthy controls after acupuncture at TE5:Compared with healthy controls, patients with relatively enhanced activate brain regions in the right side of the left and right brain after acupuncture, the left is more concentrated in BA5,6,7,18,19,24,32, as well as the hypothalamus the bottom; more concentrated distribution in BA4,6,7,18,19and32. Activated relatively weakened areas of the brain are mainly distributed in the left, more concentrated in BA13, the lower part of the insular lobe, the back of tonsil of cerebellum, below the thalamus, corpus albicans, hypothalamus below the anterior lobe of the ventral posterior lateral nucleus and the peak anterior lobe; mainly focused on regions BA13of right brain.
Differences in deactivated brain areas between stroke patients and healthy controls after acupuncture at TE5:Compared with healthy controls, the relative enhancement of patient deactivation brain regions are distributed in the left and right brain after acupuncture, the left is more concentrated in BA6,11,20,22,37,47, and front lingula of cerebellum, the back of the cerebellar tonsils and the peak anterior lobe of cerebellum; right side is more concentrated in BA8,37,45,47, as well as the peak anterior lobe of cerebellum, the front of the cerebellum nodules, below the lenticular nucleus leaves, outside of the globus pallidus, the bottom of the temporal lobe and hippocampal gyrus. Deactivate brain regions relative weakening of the left brain area BA7.
Conclusion
By comparing This study preliminary indicated there are some differences among the acupuncture TE5and sham acupuncture, acupuncture TE5and non-acupoints, acupuncture TE5between normal subjects and patients with ischemic stroke; At the same time, the study shows that acupuncture TE5specificity directional activation/deactivations, it may be one of the mechanisms of TE5treatment of ischemic stroke movement disorders, sensory impairments, visual impairments and the aphasia, also preliminary corroborated central regulation of acupuncture TE5is to implement network-based regulation.
引文
[1]李郭梦寒,徐玉东,王宇,等.针灸在西欧的发展现状[J].长春中医药大学学报,2011,27(02)：307-309.
[2]何巍,童元元,赵英凯,等.基于国外文献的针灸适应症分析[J].针刺研究,2012,37(05)：428-430.
[3]董国锋,武晓冬,韩焱晶,等.针灸知识产权基本问题研究[J].针刺研究,2011,36(06)：457-460.
[4]Rotety T. How widely is acupuncture used in the United States [OL]. [2003-07-04]. http://nccam.Nih.gov/health/acupuncture.
[5]王富春.针灸推拿学科成为一级学科的可行性分析[J].中国针灸,2012,32(10)：868.
[6]国家中医药管理局国际合作司.中医药国际交流与合作的进展[J].中医药管理杂志,2005,13(02)：14-16.
[7]杜元灏,李晶,孙冬纬,等.中国现代针灸病谱的研究[J].中国针灸,2007,27(05)：373-378.
[8]杜元灏,黄卫,熊俊,等.国外针灸病谱的初步研究[J].中国针灸,2009,29(01)：53-55.
[9]李江慧,宿杨帅,景向红,等.对国外大规模针灸临床疗效系统评价报告的分析[J].中国针灸,2011,31(07)：666.
[10]沈学勇.经络腧穴学[M].北京：中国中医药出版社,2010：18,171-172.
[11]陈凌,姚志芳.针刺胃经下肢段及非经非穴点对胃电的影响[J].福建中医药学院学报,2008,18(03)：40-42.
[12]魏育林,孔晶,刘国玲,等.健康女大学生下肢脾、胃经腧穴宫音声波接收差异性观察[J].北京中医药杂志,2010,29(04)：252-254.
[13]于岩瀑.针刺三阴交、悬钟对原发性痛经患者子宫动脉血流的影响[D].山东：山东中医药大学,2007：1-51.
[14]路玫,张宝旬,赵丽娜,等.健康人十二井穴皮肤温度差异的比较[J].针刺研究,2011,36(02)：132-135.
[15]王利春,王志勇,康西忠,等.不同针刺方法对中风患者手痉挛影响的对比研究[J].中国针灸,2008,28(07)：503-506.
[16]徐福,宣丽华,张舒雁,等.针刺不同穴位组合降低血脂的临床研究[J].中华中医药学刊,2009,27(03)：557-559.
[17]李艳梅.不同时间温针灸对老年人超氧化物歧化酶、T细胞亚群的影响[J].中医杂志,2011,52(21)：1840-1842.
[18]李凌鑫,孟智宏,樊小农,等.经穴效应特异性研究进展[J].中国针灸,2011,31(11)：1054.
[19]王德军,严洁,常小荣,等.经穴效应特异性研究现状与展望[J].世界中医药,2011,6(04)：366.
[20]孙世伟,王舒.经穴特异性研究概况[J].山西中医,2012,28(05)：40.
[21]赖新生,黄泳.经穴-脑相关假说指导下经穴特异性、针刺得气、配伍规律脑功能界定[J].中国针灸,2007,27(10)：779.
[22]张毅.基于ICA方法的针刺效应网络研究[D].西安：西安电子科技大学,2009：7.
[23]包尚联.脑功能成像物理学[M].郑州：郑州大学出版社,2006：176.
[24]赵志奇.现代神经科学技术研究[M].北京：科学出版社,2006：953.
[25]苏世君,赵晓峰,王舒.脑功能成像技术在穴位特异性研究中的应用[J].中国针灸,2010,30(12)：997-1000.
[26]田德禄.中医内科学[M].北京：人民卫生出版社,2009：269-271.
[27]石学敏.针灸治疗学[M].北京：人民卫生出版社,2009：207-220.
[28]王维治,罗祖明.神经病学[M].北京：人民卫生出版社,2009：126-131.
[29]蔡宏伟.针灸治疗中风病的临床文献研究[D].广州：广州中医药大学,2011：13-15,22,42.
[30]吴广伟.针刺治疗缺血性中风30例[J].上海针灸杂志,2007,26(02)：2.
[31]吕宏.电针为主治疗缺血性中风162例[J].湖南中医杂志,2007,23(04)：47-48.
[32]何扬子,曾纪伟,吴丽红,等.项针治疗缺血性中风的临床观察[J].暨南大学学报(自然科学与医学版),2010,31(04)：411-417.
[33]张晶,田思胜.对《针灸大成》中风记载的分析[J].山东中医药大学学报,2012,36(03)：220-222.
[34]梁永瑛,徐平.针灸治疗中风偏瘫选穴规律研究[J].上海针灸杂志,2007,126(10)：28.
[35]曾统军.外关穴特异性的fMRI脑功能成像研究[D].广州：南方医科大学,2009： 19-24.
[36]国家中医药管理局脑病急症科研组.中风辨证诊断标准(试行)[J].北京中医药大学学报,1996,19(01)：55-56.
[37]中华神经科学会、中华神经外科学会.各类脑血管疾病诊断要点[J].中华神经科杂志,1996,29(06)：379-380.
[38]Sun TK, Chiu SC, Yeh SH, et al. Assessing reliability and validity of the Chinese version of the stroke scale:scale development [J]. Int J Nurs Stud.2006;43(4):457-463.
[39]仲来福.卫生学[M].北京：人民卫生出版社,2006：97
[40]中华人民共和国国家质量监督检疫检验总局,中国国家标准化管理委员会.腧穴名称与定位：中华人民共和国国家标准[M].北京：中国标准出版社,2006,GB/T12346,2006：27.
[41]Talairach J, Tournoux P. Co-planar stereotaxic atlas of t he human brain [M]. New York: Thieme,1988:11-20.
[42]Nopperncy U, Price CJ. Functional imaging of the semantic system:Retrieval of sensory-experienced and verbally learned knowledge[J]. Brain and Language,2003, 84(1):120-133.
[43]田小明.中医在美国发展的概况[J].北京大学学报(医学版),2012,44(05)：715-719.
[44]王淑友,张栋,朱元根,等.穴位温度与电阻相关关系的研究[J].辽宁中医杂志,2007,34(01)：5-6.
[45]赵宁侠,郭瑞林,任秦有,等.针刺肺俞穴及非经非穴点对肺功能影响的对照研究[J].中国针灸,2003,23(08)：461-462.
[46]许金森,潘晓华,胡翔龙,等.督脉循行线上及其左右两侧旁开对照点微循环血流灌注量的比较[J].针刺研究,2008,33(05)：321-325.
[47]Chou Che-yi,Cheng Yu Wen,Kao Min-Tsung and Huang Chiu-Ching. Acupuncture in haemodialysis patients at the Quchi (LI 11) acupoint for refractory uraemic pruritu[J]. Nephrol Dial Transplant,2005,20 (09):1912-1915.
[48]程凯.针刺小肠经不同经穴对听性脑干反应影响的特异性研究[J].北京中医药大学学报,2003,26(02)：79-80.
[49]陈采益,徐斌,喻晓春,等.电针经穴与相应非经穴对大鼠心动过缓调节效应差异的研究[J].上海针灸杂志,2010,29(12)：747-751.
[50]岑珏,陈跃来,哈力甫,等.会阳穴治疗不稳定膀胱的特异性研究[J].上海中医 药杂志,2007,41(02)：38-40.
[51]刘俊岭,陈淑萍,高永辉.电针不同穴位对大鼠子宫平滑肌电活动的影响[J].针刺研究,2007,32(04)：237-242.
[52]魏育林,屠亦文,梁甜甜,等.宫调体感音乐声波在健康人体内传导的实验研究[J].中国针灸,2005,25(02)：111-114.
[53]蔡荣林,胡玲,吴子建,等.针刺不同经穴对正常人事件相关电位P3a和P3b的影响[J].中西医结合学报,2012,10(01)：48-53.
[54]任晓暄,郭孟玮,赵雅芳,等.电针三阴交穴和血海穴对实验性类痛经大鼠痛调节机制的影响[J].中医药学报,2011,39(06)：15-20.
[55]徐冬梅,杨启亮.胃经五输穴各穴位阻抗值趋势初探[J].贵阳医学杂志,2011,35(07)：599-601.
[56]王德军,常小荣,严洁,等.针刺足阳明胃经特定穴与非特定穴治疗功能性消化不良疗效比较[J].中国针灸,2012,32(08)：703-707.
[57]魏媛媛,樊小农,王舒,等.水沟穴干预MCAO大鼠脑梗死面积的特异性效应及针刺参数研究[J].中国针灸,2010,30(03)：221-225.
[58]张翠彦,王寅.深刺与浅刺治疗突发性耳聋的疗效观察[J].中国针灸,2006,26(04)：256-258.
[59]熊瑾,刘芳,王伟,等.得气、针刺手法与针刺治疗原发性痛经疗效的关系[J].辽宁中医杂志,2011,38(08)：1482-1485.
[60]韩健.针刺鱼际穴对支气管哮喘患者肺功能的影响及即刻平喘效应观察[J].中国针灸,2012,32(10)：891-893.
[61]胡玲,何璐,蔡荣林,等.电针不同单穴与原络配穴对急性心肌缺血家兔心功能及心肌酶的影响[J].针刺研究,2010,35(05)：363-36.
[62]吴巧凤,毛森,蔡玮,等.针刺俞、募穴对功能性消化不良大鼠血清大分子代谢产物的影响[J].针刺研究,2010,35(04)：287-292.
[63]王艳丽.心包俞募配穴协同拮抗作用的临床研究[J].上海针灸杂志,2005,24(06)：29.‘
[64]高骏,刘旭光,余曙光,等.关于腧穴“动态性”的初步探讨[J].中国针灸,2010,30(08)：643-645.
[65]余芝,夏有兵,卢明香,等.电针不同部位单穴对大鼠胃运动双向调节效应特征的研究[J].时珍国医国药,2012,23(11)：2881-2883.
[66]陈高彰,毕国伟,卢政男,等.过敏性鼻炎病人与正常人的穴位良导络值比较研究[J].成都中医药大学学报,2010,33(02)：33-34.
[67]佘延芬,孙立虹,李新华,等.原发性痛经患者三阴交穴电阻值变化规律的研究[J].北京中医药大学学报,2010,33(07)：496-499.
[68]钟海珍,常静玲,朱丹,等.针刺效应的脑功能磁共振成像研究进展[J].针刺研究,2012(02)：161.
[69]田捷,刘一军.基于时空编码脑网络的针刺穴位组学研究[J].科学中国人,2010(05)：50-52.
[70]王爱成,王玉来,单保慈,等.针刺申脉穴的fMRI脑功能成像研究[J].针刺研究,2005,30(01)：43-47.
[71]王葳,李坤成,单保慈,等.针刺正常老年人“四关穴”的脑功能MRI研究[J].中国医学影像技术,2006,22(06)：829-833.
[72]吴志远,缪飞,项琼瑶,等.针刺同一经络不同穴位的磁共振脑功能成像对比研究[J].中国医学影像学杂志,2008,16(02)：101-105.
[73]龙玉,刘波,刘现,等.静息态功能磁共振评价针刺足三里穴后效应[J].中枢神经影像学,2009,25(03)：373-376
[74]刘波,刘舰,陈俊,等.针刺穴位和非穴位对脑功能连接影响的MR研究[J].中国针灸,2009,29(12)：981-985.
[75]钟治平,吴珊珊,刘波,等.腹针“补肾填髓”法静息状态脑功能成像研究[J].中国针灸,2011,31(02)：139-143.
[76]韩俊洲,徐海波,唐宏图,等.电针周围性面瘫患者合谷穴的功能磁共振成像研究[J].中国医学影像技术,2008,24(03)：336-340.
[77]李霁,张俊海,董竞成.针刺镇痛对坐骨神经痛患者脑功能成像的影响[J].上海针灸杂志,2007,26(08)：3-5.
[78]崔方圆,王朋,谭中建,等.头针顶颢前斜线治疗中风病即刻疗效的临床观察和fMRI研究[A].国家中医药管理局脑病重点研究室建设研讨会暨中风病科研成果推广交流会论文集[C],2010：134-141.
[79]杨骏,李传富,张庆萍,等.合谷穴针刺周围性面瘫患者脑功能成像初步分析[J].长春中医药大学学报,2012(04)：608.
[80]戴西件,高磊,龚洪翰,等.静息态功能磁共振低频振幅技术评价睡眠剥夺下针刺三阴交后效应[J].中国针灸,2012,32(01)：47-52.
[81]蒋萃.针刺经穴与非穴治疗偏头痛的效应及功能磁共振成像研究[D].四川：成都中医药大学,2012：3-5.
[82]金香兰.针刺足三里穴FDG-PET和fMRI脑功能成像研究[D].北京：中国人民解放军军医进修学院,2005：3-4.
[83]Chen YI, W ang FN, Nelson AJ, et al. Electrical stimulation modulates the ampheta mine-induced hemodynamic changes:an fMRI study to compare the effect o f stimulating location, and frequencies on rats [J]. Neurosci Lett,2008,444 (02): 117-121.
[84]付平,贾建平,朱江,等.针刺内关穴对机体不同功能状态下fMRI脑功能成像的影响[J].中国针灸,2005,25(11)：784-786.
[85]付平,贾建平,王葳,等.电针内关和神门穴对脑功能成像不同影响的观察[J].中国针灸,2005,25(01)：61-63.
[86]黄泳,唐安戊,李求实,等.针刺神门穴的相对特异性作用的脑功能成像研究[J].成都中医药大学学报,2007,30(03)：6-9.
[87]邸新,饶恒毅.人脑功能连通性研究进展[J].生物化学与生物物理进展,2007,34(01)：5-12.
[88]魏海峰,伍建林.BOLD-fMRI实验技术方法及后处理研究进展[J].中国中西医结合影像学杂志,2008,6(01)：51-54.
[89]方继良,王小玲.脑功能磁共振成像技术简介及针刺研究应用[J].中国中西医结合影像学杂志,2012,10(01)：95.
[90]贾建平.神经病学[M].北京：人民卫生出版社,2011：175-187.
[91]赵建国.脑梗死[M].北京：人民卫生出版社,2006：6-49.
[92]白晶,李宝栋,唐强,等.头穴丛刺法对急性缺血性脑梗死大鼠神经可塑性影响的实验研究[J].针灸临床杂志,2005,21(06)：47-48.
[93]刘智斌,牛文民.“嗅三针”电刺激对脑缺血再灌注大鼠神经元线粒体保护作用的观察[J].针刺研究,2007,32(03)：163-166.
[94]李铁浪,严洁,常小荣,等.电针不同穴组对急性脑缺血大鼠行为学评分和脑梗死体积的影响[J].中医药导报,2007,13(02)：5-8.
[95]徐放明,郭义,陈爽白.针刺手三阳井穴对急性缺氧小白鼠影响的观察[J].南京中医药大学学报(自然科学版),2005,21(04)：245-246.
[96]石现,左芳,田嘉禾.针刺头穴对中风患者大脑运动功能区糖代谢的影响[J].针刺 研究,2005,30(03)：167-170.
[97]孟智宏,杜元灏,石学敏.脑梗死大鼠脑、肺组织及血液中能量代谢指标变化及针刺的干预作用[J].中国临床康复,2005,9(45)：96-98.
[98]远慧茹,刘存志,于建春,等.调神益气针法对多发梗死性痴呆大鼠脑内兴奋性氨基酸含量变化的影响[J].中国临床康复,2005,21(02)：127-129.
[99]姚凯,郭义,胡利民,等.针刺对大鼠脑缺血超早期脑细胞内外游离钙离子浓度的影响[J].中国中西医结合急救杂志,2005,12(05)：303-305.
[100]张金铃,郭莹,李瑞午,等.针刺血清对缺血再灌注模型大鼠海马神经元钙超载的保护作用[J].中国针灸,2009,29(01)：45-47.
[101]袁红,宋颖,欧翔,等.电针对局灶性脑缺血再灌注大鼠IL-6、L-10表达影响的实验研究[J].北京中医药大学学报(中医临床版),2006,13(04)：18-21.
[102]季杰,刘慧林,程金莲,等.三通法针刺对急性缺血性脑血管病患者血清TNF-α及IL-1 β的影响[J].中国中西医结合杂志,2006,26(06)：500-503.
[103]任玉录,孙德俊.电针对局灶性脑缺血急性期大鼠脑组织中自由基水平影响和神经功能相关性的实验研究[J].中西医结合心脑血管病杂志,2008,6(06)：679-681.
[104]王世军,崔可密,卢岩,等.针刺对MCAO大鼠血NO、ET的影响[J].山东中医药大学学报,2005,3(29)：159-161.
[105]穆艳云,李忠仁,牛文民,等.电针对局灶性脑缺血再灌注大鼠纹状体线粒体ATP酶与总体抗氧化能力的影响[J].上海针灸杂志,2007,26(01)：42-44.
[106]刘玉珍,韩景献,蒋戈利,等.电针对大鼠脑缺血再灌注模型P-选择素和E-选择素表达影响的实验研究[J].时珍国医国药,2007,18(01)：79-81.
[107]刘玉珍,韩景献,蒋戈利,等.针刺对脑缺血再灌注大鼠P-选择素和E-选择素蛋白表达影响的实验研究[J].四川中医,2007,25(01)：14-16.
[108]王春霞,孙远征.头穴丛刺法对慢性脑缺血大鼠海马血管内皮生长因子表达的影响[J].针刺研究,2012,37(05)：375-379.
[109]陈少宗,胡浩,卜彦青.电针疗法对脑梗塞患者TXB2、PGF1 α的影响与其基础状态的数量关系[J].中国中医药科技,2008,15(03)：166-167.
[110]熊伟,黄光英.针刺对局部脑缺血大鼠大脑皮层基质金属蛋白酶-2表达的影响[J].中国康复,2007,22(03)：147-149.
[111]陈睿,王光义.针刺对脑缺血大鼠大脑皮质胰岛素样生长因子-1表达的影响[J].辽宁中医药大学学报,2007,9(05)：180-181.
[112]倪金霞,朱文增,唐强,等.头穴丛刺法对急性脑梗死大鼠病理学及神经生长因子和转化生长因子的影响[J].中国康复理论与实践,2007,13(06)：522-523.
[113]吴绪平,罗惠平,黄伟,等.针刺治疗急性脑梗死临床观察[J].针灸临床杂志,2008,17(08)：1195-1197.
[114]丁昀,吴绪平,黄伟,等.针刺对急性脑梗死患者血浆D-二聚体和纤维蛋白原含量的影响[J].湖北中医学院学报,2007,9(02)：13-15.
[115]李淑萍,薛茜,石武年,等.醒脑针刺法对急性脑梗死患者血浆中β-内啡肽含量的影响[J].中国中医药信息杂志,2006,13(04)：70.
[116]张红星,周利,张唐法.头针治疗脑卒中对相关血生化指标的影响[J].中国临床康复,2006,10(19)：9-11.
[117]倪金霞,高维滨,朱文增,等.项针疗法对急性脑梗死大鼠病理学及bcl-2表达的影响[J].针灸临床杂志,2007,23(06)：46-47.
[118]倪金霞,朱文增,于致顺.头穴丛刺法对急性脑梗死大鼠病理形态学及凋亡相关基因Caspase-3的影响[J].上海针灸杂志,2008,27(09)：43-45.
[119]范郁山,黄婕,谭小华,等.浅刺针法对脑梗塞大鼠脑组织缺血半暗带Fas、Bcl-2蛋白表达的影响[J].针灸临床杂志,2008,24(08)：44-47.
[120]赵宇辉,孙忠人.针灸预处理对心肌缺血／再灌注大鼠细胞凋亡及相关基因表达的影响[J].心脏杂志,2009,21(05)：657-659.
[121]Zhao Yu-hui, Sun Zhong-ren. Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats[J]. J Acupunct Tuina Sci,2009,7(02):71-74.
[122]贾少微,王全师,徐文贵,等.应用PET研究针刺信号对人脑能量代谢的影响[J].中国中西医结合杂志,2002,22(07)：508.
[123]李霁,左传涛,管一晖,等.针刺对脑梗塞患者脑内葡萄糖代谢的影响[J].中国中西医结合杂志,2002,22(10)：741.
[124]任延革(点校).黄帝内经灵枢经新校版[M].北京：人民军医出版社,2006：97,147,229.
[125]李宁(点校).扁鹊神应针灸玉龙经和神应经[M].北京：中医古籍出版社,2008：63,119.
[126]杨宇华,李俊滔.针刺配合推拿治疗颈椎病颈痛100例的疗效观察[A].广东：广东省针灸学会第十一次学术研讨会论文汇编[C],2010：292.
[127]孙洽熙,孙峰(整理).素问病机气宜保命集[M].北京：人民卫生出版社,2005：41.
[128]李红香.基于中医文献的中风病研究[D].南京：南京中医药大学,2011：44-45.
[129]王启才.针灸治疗学[M].北京：中国中医药出版社,2011：66-69.
[130]牛昱光.针灸治疗中风病的现代临床文献研究[D].山东：山东中医药大学,2011：44-45.
[131]黄泳,王升旭.针灸临床实用新型技术[M].广州：暨南大学出版社,2008：119-129.
[132]陆寿康、孙尧其.实用头针大全[M].上海：上海科技出版社,2011：46-50.
[133]李勇.中渚、外关穴治疗中风偏瘫上肢远端水肿的疗效观察.针灸临床杂志,1996,12(05)： 79.
[134]彭冬青.针灸治疗中风偏瘫980例疗效观察[J].北京中医杂志,2003,22(02)：38.
[135]Zhu XM, Polus B. A controlled trial on acupuncture for chronic neckpain [J]. AmJ ChinMed,2002,30(01):13-28.
[136]Zaslawski CJ, CobbinD, Lidums E, et al. The impact of site specificity andneedle manipulationonchanges to pain pressure threshold following manual acupuncture:a controlledstudy[J]. Complement Ther Med,2003,11 (01):11-21.
[137]顾星.针刺合谷穴对脑磁图的动态观察[J].上海针灸杂志,2005,24(07)：38-40.
[138]Lee MS, Jeong SY, LeeYJ, et al. Differences in Electrical conduction properties between meridians and non-meridians[J]. AmJ ChinMed,2005,33(05):,723-728.
[139]黄聪阳,胡翔龙,阮传亮,等.足太阳膀胱经整体性功能的临床研究[J].上海针灸杂志,2005,24(4)：27-29.
[140]胡卡明,王承平,谢慧君,等.针刺穴位与非穴位激活不同脑区的效应观察[J].中国针灸,2006,26(3)：205-207.
[141]Kong J, Gollub RL, Webb JM, et al. Test-retest study of fMRI signal change evoked by electro acupuncture stimulation[J]. Neuroimage,2007,34(03):1171-1181.
[142]刘波,刘岘,陈俊,等.针刺穴位和非穴位对脑功能连接影响的MR研究[J].中国针灸,2009,29(12)：981-985.
[143]杨旭光,李瑛,田小平,等.国内外针灸研究中非经非穴选取方法评述[J].中医杂志,2009,50(08)：748.
[144]汤键,杨广义,王绍瑛,等.电针对冠心病心电图ST段影响的初步探讨[J].中医药信息,1996,(05)：36.
[145]邓海平,沈雪勇,丁光宏,等.太渊穴自发红外辐射的相对特异性[J].中华中医药学刊,2008,26(03)：494-495.
[146]张云凌,赖新生.经穴体表范围测定的现状与思考[J].针灸临床杂志,2011,27(10)：50.
[147]胡翔龙,许金森,叶蕾,等.人体体表循经红外线辐射轨迹的加热诱发[J].红外与毫米波学报,2002,21(01)：6-8.
[148]艾林,戴建平,赵百孝,等.针刺镇痛机制的功能磁共振成像磁共振对照研究[J].中国医学影像技术,2004,20(08)：1197-1200.
[149]Kim KS, Nam YM. The analgesic effects of capsicum plaster at the Zusanli point after abdominal hysterectomy [J]. AnesthAnalg,2006,103(03):709-713.
[150]Maioli C, Falciati L, Marangon M, et al. Short-termand long-term modulation of upper limb motor-evoked potentials induced by acupuncture[J]. Eur J Neurosci,2006, 23(07):1931-1938.
[151]Margolin A, Chang P, Avants SK, et al. Effects of sham and real auricular needling: implications for trials of acupuncture for cocaine addition[J]. Am J Chinese Med,1993, 21(02):103-111.
[152]Tang XW. Cerebral function image [M]. Hefei:University of Science and Technology of China Press,1999:1-239.
[153]Hui K K, Liu J, Makris N, et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain:evidence from fMRI studies in normal subjects [J]. Hum Brain Mapp,2000,9(l):13-25.
[154]陈华, 杨丰, 黄泳,等.SPM在外关穴针刺脑功能成像中的应用研究[J].中国医学物理学杂志,2011,28(01)：2369-2372.
[155]邱文娟.脑功能磁共振成像数据的相关性研究[D].河南：解放军信息工程大学,2011：2,11.
[156]Ogawa S,Lee TM,Kay AR,et al.Brain magnetic resonance imaging with contrast dependent on blood oxygenation[J].Proc.Natl.Acad.Sci.1990,87(24):9868-9872.
[157]钟世镇.系统解剖学[M].北京：高等教育出版社,2007： 288-316.
[158]柏树令.系统解剖学[M].北京：人民卫生出版社,2010：314-376.
[159]Poldrack RA, Wagner AD, Prull M W, etal. Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex [J]. Neuro Image,1999,10: 15-35.
[160]谢春明,马林,方艳,等.线索诱发海洛因渴求的功能磁共振成像研究[J].中国医学影像技术,2006,22(11)：1642-1645.
[161]Bai L, Qin W, T ian J, etal. Time-varied characteristics of acupuncture effects in fMRI studies [J]. Hum Brain Mapp,2009,30(11):3445-3460.
[162]Napadow V, Dhond R P, Kim J, et al. Brain encoding of acupunctur e sensation-coupling on-line rating with fMRI [J]. Neur oimag e,2009,47 (3):1055-1065.
[163]张贵锋,黄泳,唐纯志,等.针刺得气的PET脑功能成像研究[J].针刺研究,2011,36(01)：46-51.
[2]何巍,童元元,赵英凯,等.基于国外文献的针灸适应症分析[J].针刺研究,2012,37(05)：428-430.
[3]董国锋,武晓冬,韩焱晶,等.针灸知识产权基本问题研究[J].针刺研究,2011,36(06)：457-460.
[4]Rotety T. How widely is acupuncture used in the United States [OL]. [2003-07-04]. http://nccam.Nih.gov/health/acupuncture.
[5]王富春.针灸推拿学科成为一级学科的可行性分析[J].中国针灸,2012,32(10)：868.
[6]国家中医药管理局国际合作司.中医药国际交流与合作的进展[J].中医药管理杂志,2005,13(02)：14-16.
[7]杜元灏,李晶,孙冬纬,等.中国现代针灸病谱的研究[J].中国针灸,2007,27(05)：373-378.
[8]杜元灏,黄卫,熊俊,等.国外针灸病谱的初步研究[J].中国针灸,2009,29(01)：53-55.
[9]李江慧,宿杨帅,景向红,等.对国外大规模针灸临床疗效系统评价报告的分析[J].中国针灸,2011,31(07)：666.
[10]沈学勇.经络腧穴学[M].北京：中国中医药出版社,2010：18,171-172.
[11]陈凌,姚志芳.针刺胃经下肢段及非经非穴点对胃电的影响[J].福建中医药学院学报,2008,18(03)：40-42.
[12]魏育林,孔晶,刘国玲,等.健康女大学生下肢脾、胃经腧穴宫音声波接收差异性观察[J].北京中医药杂志,2010,29(04)：252-254.
[13]于岩瀑.针刺三阴交、悬钟对原发性痛经患者子宫动脉血流的影响[D].山东：山东中医药大学,2007：1-51.
[14]路玫,张宝旬,赵丽娜,等.健康人十二井穴皮肤温度差异的比较[J].针刺研究,2011,36(02)：132-135.
[15]王利春,王志勇,康西忠,等.不同针刺方法对中风患者手痉挛影响的对比研究[J].中国针灸,2008,28(07)：503-506.
[16]徐福,宣丽华,张舒雁,等.针刺不同穴位组合降低血脂的临床研究[J].中华中医药学刊,2009,27(03)：557-559.
[17]李艳梅.不同时间温针灸对老年人超氧化物歧化酶、T细胞亚群的影响[J].中医杂志,2011,52(21)：1840-1842.
[18]李凌鑫,孟智宏,樊小农,等.经穴效应特异性研究进展[J].中国针灸,2011,31(11)：1054.
[19]王德军,严洁,常小荣,等.经穴效应特异性研究现状与展望[J].世界中医药,2011,6(04)：366.
[20]孙世伟,王舒.经穴特异性研究概况[J].山西中医,2012,28(05)：40.
[21]赖新生,黄泳.经穴-脑相关假说指导下经穴特异性、针刺得气、配伍规律脑功能界定[J].中国针灸,2007,27(10)：779.
[22]张毅.基于ICA方法的针刺效应网络研究[D].西安：西安电子科技大学,2009：7.
[23]包尚联.脑功能成像物理学[M].郑州：郑州大学出版社,2006：176.
[24]赵志奇.现代神经科学技术研究[M].北京：科学出版社,2006：953.
[25]苏世君,赵晓峰,王舒.脑功能成像技术在穴位特异性研究中的应用[J].中国针灸,2010,30(12)：997-1000.
[26]田德禄.中医内科学[M].北京：人民卫生出版社,2009：269-271.
[27]石学敏.针灸治疗学[M].北京：人民卫生出版社,2009：207-220.
[28]王维治,罗祖明.神经病学[M].北京：人民卫生出版社,2009：126-131.
[29]蔡宏伟.针灸治疗中风病的临床文献研究[D].广州：广州中医药大学,2011：13-15,22,42.
[30]吴广伟.针刺治疗缺血性中风30例[J].上海针灸杂志,2007,26(02)：2.
[31]吕宏.电针为主治疗缺血性中风162例[J].湖南中医杂志,2007,23(04)：47-48.
[32]何扬子,曾纪伟,吴丽红,等.项针治疗缺血性中风的临床观察[J].暨南大学学报(自然科学与医学版),2010,31(04)：411-417.
[33]张晶,田思胜.对《针灸大成》中风记载的分析[J].山东中医药大学学报,2012,36(03)：220-222.
[34]梁永瑛,徐平.针灸治疗中风偏瘫选穴规律研究[J].上海针灸杂志,2007,126(10)：28.
[35]曾统军.外关穴特异性的fMRI脑功能成像研究[D].广州：南方医科大学,2009： 19-24.
[36]国家中医药管理局脑病急症科研组.中风辨证诊断标准(试行)[J].北京中医药大学学报,1996,19(01)：55-56.
[37]中华神经科学会、中华神经外科学会.各类脑血管疾病诊断要点[J].中华神经科杂志,1996,29(06)：379-380.
[38]Sun TK, Chiu SC, Yeh SH, et al. Assessing reliability and validity of the Chinese version of the stroke scale:scale development [J]. Int J Nurs Stud.2006;43(4):457-463.
[39]仲来福.卫生学[M].北京：人民卫生出版社,2006：97
[40]中华人民共和国国家质量监督检疫检验总局,中国国家标准化管理委员会.腧穴名称与定位：中华人民共和国国家标准[M].北京：中国标准出版社,2006,GB/T12346,2006：27.
[41]Talairach J, Tournoux P. Co-planar stereotaxic atlas of t he human brain [M]. New York: Thieme,1988:11-20.
[42]Nopperncy U, Price CJ. Functional imaging of the semantic system:Retrieval of sensory-experienced and verbally learned knowledge[J]. Brain and Language,2003, 84(1):120-133.
[43]田小明.中医在美国发展的概况[J].北京大学学报(医学版),2012,44(05)：715-719.
[44]王淑友,张栋,朱元根,等.穴位温度与电阻相关关系的研究[J].辽宁中医杂志,2007,34(01)：5-6.
[45]赵宁侠,郭瑞林,任秦有,等.针刺肺俞穴及非经非穴点对肺功能影响的对照研究[J].中国针灸,2003,23(08)：461-462.
[46]许金森,潘晓华,胡翔龙,等.督脉循行线上及其左右两侧旁开对照点微循环血流灌注量的比较[J].针刺研究,2008,33(05)：321-325.
[47]Chou Che-yi,Cheng Yu Wen,Kao Min-Tsung and Huang Chiu-Ching. Acupuncture in haemodialysis patients at the Quchi (LI 11) acupoint for refractory uraemic pruritu[J]. Nephrol Dial Transplant,2005,20 (09):1912-1915.
[48]程凯.针刺小肠经不同经穴对听性脑干反应影响的特异性研究[J].北京中医药大学学报,2003,26(02)：79-80.
[49]陈采益,徐斌,喻晓春,等.电针经穴与相应非经穴对大鼠心动过缓调节效应差异的研究[J].上海针灸杂志,2010,29(12)：747-751.
[50]岑珏,陈跃来,哈力甫,等.会阳穴治疗不稳定膀胱的特异性研究[J].上海中医 药杂志,2007,41(02)：38-40.
[51]刘俊岭,陈淑萍,高永辉.电针不同穴位对大鼠子宫平滑肌电活动的影响[J].针刺研究,2007,32(04)：237-242.
[52]魏育林,屠亦文,梁甜甜,等.宫调体感音乐声波在健康人体内传导的实验研究[J].中国针灸,2005,25(02)：111-114.
[53]蔡荣林,胡玲,吴子建,等.针刺不同经穴对正常人事件相关电位P3a和P3b的影响[J].中西医结合学报,2012,10(01)：48-53.
[54]任晓暄,郭孟玮,赵雅芳,等.电针三阴交穴和血海穴对实验性类痛经大鼠痛调节机制的影响[J].中医药学报,2011,39(06)：15-20.
[55]徐冬梅,杨启亮.胃经五输穴各穴位阻抗值趋势初探[J].贵阳医学杂志,2011,35(07)：599-601.
[56]王德军,常小荣,严洁,等.针刺足阳明胃经特定穴与非特定穴治疗功能性消化不良疗效比较[J].中国针灸,2012,32(08)：703-707.
[57]魏媛媛,樊小农,王舒,等.水沟穴干预MCAO大鼠脑梗死面积的特异性效应及针刺参数研究[J].中国针灸,2010,30(03)：221-225.
[58]张翠彦,王寅.深刺与浅刺治疗突发性耳聋的疗效观察[J].中国针灸,2006,26(04)：256-258.
[59]熊瑾,刘芳,王伟,等.得气、针刺手法与针刺治疗原发性痛经疗效的关系[J].辽宁中医杂志,2011,38(08)：1482-1485.
[60]韩健.针刺鱼际穴对支气管哮喘患者肺功能的影响及即刻平喘效应观察[J].中国针灸,2012,32(10)：891-893.
[61]胡玲,何璐,蔡荣林,等.电针不同单穴与原络配穴对急性心肌缺血家兔心功能及心肌酶的影响[J].针刺研究,2010,35(05)：363-36.
[62]吴巧凤,毛森,蔡玮,等.针刺俞、募穴对功能性消化不良大鼠血清大分子代谢产物的影响[J].针刺研究,2010,35(04)：287-292.
[63]王艳丽.心包俞募配穴协同拮抗作用的临床研究[J].上海针灸杂志,2005,24(06)：29.‘
[64]高骏,刘旭光,余曙光,等.关于腧穴“动态性”的初步探讨[J].中国针灸,2010,30(08)：643-645.
[65]余芝,夏有兵,卢明香,等.电针不同部位单穴对大鼠胃运动双向调节效应特征的研究[J].时珍国医国药,2012,23(11)：2881-2883.
[66]陈高彰,毕国伟,卢政男,等.过敏性鼻炎病人与正常人的穴位良导络值比较研究[J].成都中医药大学学报,2010,33(02)：33-34.
[67]佘延芬,孙立虹,李新华,等.原发性痛经患者三阴交穴电阻值变化规律的研究[J].北京中医药大学学报,2010,33(07)：496-499.
[68]钟海珍,常静玲,朱丹,等.针刺效应的脑功能磁共振成像研究进展[J].针刺研究,2012(02)：161.
[69]田捷,刘一军.基于时空编码脑网络的针刺穴位组学研究[J].科学中国人,2010(05)：50-52.
[70]王爱成,王玉来,单保慈,等.针刺申脉穴的fMRI脑功能成像研究[J].针刺研究,2005,30(01)：43-47.
[71]王葳,李坤成,单保慈,等.针刺正常老年人“四关穴”的脑功能MRI研究[J].中国医学影像技术,2006,22(06)：829-833.
[72]吴志远,缪飞,项琼瑶,等.针刺同一经络不同穴位的磁共振脑功能成像对比研究[J].中国医学影像学杂志,2008,16(02)：101-105.
[73]龙玉,刘波,刘现,等.静息态功能磁共振评价针刺足三里穴后效应[J].中枢神经影像学,2009,25(03)：373-376
[74]刘波,刘舰,陈俊,等.针刺穴位和非穴位对脑功能连接影响的MR研究[J].中国针灸,2009,29(12)：981-985.
[75]钟治平,吴珊珊,刘波,等.腹针“补肾填髓”法静息状态脑功能成像研究[J].中国针灸,2011,31(02)：139-143.
[76]韩俊洲,徐海波,唐宏图,等.电针周围性面瘫患者合谷穴的功能磁共振成像研究[J].中国医学影像技术,2008,24(03)：336-340.
[77]李霁,张俊海,董竞成.针刺镇痛对坐骨神经痛患者脑功能成像的影响[J].上海针灸杂志,2007,26(08)：3-5.
[78]崔方圆,王朋,谭中建,等.头针顶颢前斜线治疗中风病即刻疗效的临床观察和fMRI研究[A].国家中医药管理局脑病重点研究室建设研讨会暨中风病科研成果推广交流会论文集[C],2010：134-141.
[79]杨骏,李传富,张庆萍,等.合谷穴针刺周围性面瘫患者脑功能成像初步分析[J].长春中医药大学学报,2012(04)：608.
[80]戴西件,高磊,龚洪翰,等.静息态功能磁共振低频振幅技术评价睡眠剥夺下针刺三阴交后效应[J].中国针灸,2012,32(01)：47-52.
[81]蒋萃.针刺经穴与非穴治疗偏头痛的效应及功能磁共振成像研究[D].四川：成都中医药大学,2012：3-5.
[82]金香兰.针刺足三里穴FDG-PET和fMRI脑功能成像研究[D].北京：中国人民解放军军医进修学院,2005：3-4.
[83]Chen YI, W ang FN, Nelson AJ, et al. Electrical stimulation modulates the ampheta mine-induced hemodynamic changes:an fMRI study to compare the effect o f stimulating location, and frequencies on rats [J]. Neurosci Lett,2008,444 (02): 117-121.
[84]付平,贾建平,朱江,等.针刺内关穴对机体不同功能状态下fMRI脑功能成像的影响[J].中国针灸,2005,25(11)：784-786.
[85]付平,贾建平,王葳,等.电针内关和神门穴对脑功能成像不同影响的观察[J].中国针灸,2005,25(01)：61-63.
[86]黄泳,唐安戊,李求实,等.针刺神门穴的相对特异性作用的脑功能成像研究[J].成都中医药大学学报,2007,30(03)：6-9.
[87]邸新,饶恒毅.人脑功能连通性研究进展[J].生物化学与生物物理进展,2007,34(01)：5-12.
[88]魏海峰,伍建林.BOLD-fMRI实验技术方法及后处理研究进展[J].中国中西医结合影像学杂志,2008,6(01)：51-54.
[89]方继良,王小玲.脑功能磁共振成像技术简介及针刺研究应用[J].中国中西医结合影像学杂志,2012,10(01)：95.
[90]贾建平.神经病学[M].北京：人民卫生出版社,2011：175-187.
[91]赵建国.脑梗死[M].北京：人民卫生出版社,2006：6-49.
[92]白晶,李宝栋,唐强,等.头穴丛刺法对急性缺血性脑梗死大鼠神经可塑性影响的实验研究[J].针灸临床杂志,2005,21(06)：47-48.
[93]刘智斌,牛文民.“嗅三针”电刺激对脑缺血再灌注大鼠神经元线粒体保护作用的观察[J].针刺研究,2007,32(03)：163-166.
[94]李铁浪,严洁,常小荣,等.电针不同穴组对急性脑缺血大鼠行为学评分和脑梗死体积的影响[J].中医药导报,2007,13(02)：5-8.
[95]徐放明,郭义,陈爽白.针刺手三阳井穴对急性缺氧小白鼠影响的观察[J].南京中医药大学学报(自然科学版),2005,21(04)：245-246.
[96]石现,左芳,田嘉禾.针刺头穴对中风患者大脑运动功能区糖代谢的影响[J].针刺 研究,2005,30(03)：167-170.
[97]孟智宏,杜元灏,石学敏.脑梗死大鼠脑、肺组织及血液中能量代谢指标变化及针刺的干预作用[J].中国临床康复,2005,9(45)：96-98.
[98]远慧茹,刘存志,于建春,等.调神益气针法对多发梗死性痴呆大鼠脑内兴奋性氨基酸含量变化的影响[J].中国临床康复,2005,21(02)：127-129.
[99]姚凯,郭义,胡利民,等.针刺对大鼠脑缺血超早期脑细胞内外游离钙离子浓度的影响[J].中国中西医结合急救杂志,2005,12(05)：303-305.
[100]张金铃,郭莹,李瑞午,等.针刺血清对缺血再灌注模型大鼠海马神经元钙超载的保护作用[J].中国针灸,2009,29(01)：45-47.
[101]袁红,宋颖,欧翔,等.电针对局灶性脑缺血再灌注大鼠IL-6、L-10表达影响的实验研究[J].北京中医药大学学报(中医临床版),2006,13(04)：18-21.
[102]季杰,刘慧林,程金莲,等.三通法针刺对急性缺血性脑血管病患者血清TNF-α及IL-1 β的影响[J].中国中西医结合杂志,2006,26(06)：500-503.
[103]任玉录,孙德俊.电针对局灶性脑缺血急性期大鼠脑组织中自由基水平影响和神经功能相关性的实验研究[J].中西医结合心脑血管病杂志,2008,6(06)：679-681.
[104]王世军,崔可密,卢岩,等.针刺对MCAO大鼠血NO、ET的影响[J].山东中医药大学学报,2005,3(29)：159-161.
[105]穆艳云,李忠仁,牛文民,等.电针对局灶性脑缺血再灌注大鼠纹状体线粒体ATP酶与总体抗氧化能力的影响[J].上海针灸杂志,2007,26(01)：42-44.
[106]刘玉珍,韩景献,蒋戈利,等.电针对大鼠脑缺血再灌注模型P-选择素和E-选择素表达影响的实验研究[J].时珍国医国药,2007,18(01)：79-81.
[107]刘玉珍,韩景献,蒋戈利,等.针刺对脑缺血再灌注大鼠P-选择素和E-选择素蛋白表达影响的实验研究[J].四川中医,2007,25(01)：14-16.
[108]王春霞,孙远征.头穴丛刺法对慢性脑缺血大鼠海马血管内皮生长因子表达的影响[J].针刺研究,2012,37(05)：375-379.
[109]陈少宗,胡浩,卜彦青.电针疗法对脑梗塞患者TXB2、PGF1 α的影响与其基础状态的数量关系[J].中国中医药科技,2008,15(03)：166-167.
[110]熊伟,黄光英.针刺对局部脑缺血大鼠大脑皮层基质金属蛋白酶-2表达的影响[J].中国康复,2007,22(03)：147-149.
[111]陈睿,王光义.针刺对脑缺血大鼠大脑皮质胰岛素样生长因子-1表达的影响[J].辽宁中医药大学学报,2007,9(05)：180-181.
[112]倪金霞,朱文增,唐强,等.头穴丛刺法对急性脑梗死大鼠病理学及神经生长因子和转化生长因子的影响[J].中国康复理论与实践,2007,13(06)：522-523.
[113]吴绪平,罗惠平,黄伟,等.针刺治疗急性脑梗死临床观察[J].针灸临床杂志,2008,17(08)：1195-1197.
[114]丁昀,吴绪平,黄伟,等.针刺对急性脑梗死患者血浆D-二聚体和纤维蛋白原含量的影响[J].湖北中医学院学报,2007,9(02)：13-15.
[115]李淑萍,薛茜,石武年,等.醒脑针刺法对急性脑梗死患者血浆中β-内啡肽含量的影响[J].中国中医药信息杂志,2006,13(04)：70.
[116]张红星,周利,张唐法.头针治疗脑卒中对相关血生化指标的影响[J].中国临床康复,2006,10(19)：9-11.
[117]倪金霞,高维滨,朱文增,等.项针疗法对急性脑梗死大鼠病理学及bcl-2表达的影响[J].针灸临床杂志,2007,23(06)：46-47.
[118]倪金霞,朱文增,于致顺.头穴丛刺法对急性脑梗死大鼠病理形态学及凋亡相关基因Caspase-3的影响[J].上海针灸杂志,2008,27(09)：43-45.
[119]范郁山,黄婕,谭小华,等.浅刺针法对脑梗塞大鼠脑组织缺血半暗带Fas、Bcl-2蛋白表达的影响[J].针灸临床杂志,2008,24(08)：44-47.
[120]赵宇辉,孙忠人.针灸预处理对心肌缺血／再灌注大鼠细胞凋亡及相关基因表达的影响[J].心脏杂志,2009,21(05)：657-659.
[121]Zhao Yu-hui, Sun Zhong-ren. Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats[J]. J Acupunct Tuina Sci,2009,7(02):71-74.
[122]贾少微,王全师,徐文贵,等.应用PET研究针刺信号对人脑能量代谢的影响[J].中国中西医结合杂志,2002,22(07)：508.
[123]李霁,左传涛,管一晖,等.针刺对脑梗塞患者脑内葡萄糖代谢的影响[J].中国中西医结合杂志,2002,22(10)：741.
[124]任延革(点校).黄帝内经灵枢经新校版[M].北京：人民军医出版社,2006：97,147,229.
[125]李宁(点校).扁鹊神应针灸玉龙经和神应经[M].北京：中医古籍出版社,2008：63,119.
[126]杨宇华,李俊滔.针刺配合推拿治疗颈椎病颈痛100例的疗效观察[A].广东：广东省针灸学会第十一次学术研讨会论文汇编[C],2010：292.
[127]孙洽熙,孙峰(整理).素问病机气宜保命集[M].北京：人民卫生出版社,2005：41.
[128]李红香.基于中医文献的中风病研究[D].南京：南京中医药大学,2011：44-45.
[129]王启才.针灸治疗学[M].北京：中国中医药出版社,2011：66-69.
[130]牛昱光.针灸治疗中风病的现代临床文献研究[D].山东：山东中医药大学,2011：44-45.
[131]黄泳,王升旭.针灸临床实用新型技术[M].广州：暨南大学出版社,2008：119-129.
[132]陆寿康、孙尧其.实用头针大全[M].上海：上海科技出版社,2011：46-50.
[133]李勇.中渚、外关穴治疗中风偏瘫上肢远端水肿的疗效观察.针灸临床杂志,1996,12(05)： 79.
[134]彭冬青.针灸治疗中风偏瘫980例疗效观察[J].北京中医杂志,2003,22(02)：38.
[135]Zhu XM, Polus B. A controlled trial on acupuncture for chronic neckpain [J]. AmJ ChinMed,2002,30(01):13-28.
[136]Zaslawski CJ, CobbinD, Lidums E, et al. The impact of site specificity andneedle manipulationonchanges to pain pressure threshold following manual acupuncture:a controlledstudy[J]. Complement Ther Med,2003,11 (01):11-21.
[137]顾星.针刺合谷穴对脑磁图的动态观察[J].上海针灸杂志,2005,24(07)：38-40.
[138]Lee MS, Jeong SY, LeeYJ, et al. Differences in Electrical conduction properties between meridians and non-meridians[J]. AmJ ChinMed,2005,33(05):,723-728.
[139]黄聪阳,胡翔龙,阮传亮,等.足太阳膀胱经整体性功能的临床研究[J].上海针灸杂志,2005,24(4)：27-29.
[140]胡卡明,王承平,谢慧君,等.针刺穴位与非穴位激活不同脑区的效应观察[J].中国针灸,2006,26(3)：205-207.
[141]Kong J, Gollub RL, Webb JM, et al. Test-retest study of fMRI signal change evoked by electro acupuncture stimulation[J]. Neuroimage,2007,34(03):1171-1181.
[142]刘波,刘岘,陈俊,等.针刺穴位和非穴位对脑功能连接影响的MR研究[J].中国针灸,2009,29(12)：981-985.
[143]杨旭光,李瑛,田小平,等.国内外针灸研究中非经非穴选取方法评述[J].中医杂志,2009,50(08)：748.
[144]汤键,杨广义,王绍瑛,等.电针对冠心病心电图ST段影响的初步探讨[J].中医药信息,1996,(05)：36.
[145]邓海平,沈雪勇,丁光宏,等.太渊穴自发红外辐射的相对特异性[J].中华中医药学刊,2008,26(03)：494-495.
[146]张云凌,赖新生.经穴体表范围测定的现状与思考[J].针灸临床杂志,2011,27(10)：50.
[147]胡翔龙,许金森,叶蕾,等.人体体表循经红外线辐射轨迹的加热诱发[J].红外与毫米波学报,2002,21(01)：6-8.
[148]艾林,戴建平,赵百孝,等.针刺镇痛机制的功能磁共振成像磁共振对照研究[J].中国医学影像技术,2004,20(08)：1197-1200.
[149]Kim KS, Nam YM. The analgesic effects of capsicum plaster at the Zusanli point after abdominal hysterectomy [J]. AnesthAnalg,2006,103(03):709-713.
[150]Maioli C, Falciati L, Marangon M, et al. Short-termand long-term modulation of upper limb motor-evoked potentials induced by acupuncture[J]. Eur J Neurosci,2006, 23(07):1931-1938.
[151]Margolin A, Chang P, Avants SK, et al. Effects of sham and real auricular needling: implications for trials of acupuncture for cocaine addition[J]. Am J Chinese Med,1993, 21(02):103-111.
[152]Tang XW. Cerebral function image [M]. Hefei:University of Science and Technology of China Press,1999:1-239.
[153]Hui K K, Liu J, Makris N, et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain:evidence from fMRI studies in normal subjects [J]. Hum Brain Mapp,2000,9(l):13-25.
[154]陈华, 杨丰, 黄泳,等.SPM在外关穴针刺脑功能成像中的应用研究[J].中国医学物理学杂志,2011,28(01)：2369-2372.
[155]邱文娟.脑功能磁共振成像数据的相关性研究[D].河南：解放军信息工程大学,2011：2,11.
[156]Ogawa S,Lee TM,Kay AR,et al.Brain magnetic resonance imaging with contrast dependent on blood oxygenation[J].Proc.Natl.Acad.Sci.1990,87(24):9868-9872.
[157]钟世镇.系统解剖学[M].北京：高等教育出版社,2007： 288-316.
[158]柏树令.系统解剖学[M].北京：人民卫生出版社,2010：314-376.
[159]Poldrack RA, Wagner AD, Prull M W, etal. Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex [J]. Neuro Image,1999,10: 15-35.
[160]谢春明,马林,方艳,等.线索诱发海洛因渴求的功能磁共振成像研究[J].中国医学影像技术,2006,22(11)：1642-1645.
[161]Bai L, Qin W, T ian J, etal. Time-varied characteristics of acupuncture effects in fMRI studies [J]. Hum Brain Mapp,2009,30(11):3445-3460.
[162]Napadow V, Dhond R P, Kim J, et al. Brain encoding of acupunctur e sensation-coupling on-line rating with fMRI [J]. Neur oimag e,2009,47 (3):1055-1065.
[163]张贵锋,黄泳,唐纯志,等.针刺得气的PET脑功能成像研究[J].针刺研究,2011,36(01)：46-51.