【作者】 蒋垂刚；

【导师】 张家维；

【作者基本信息】 广州中医药大学 ， 针灸推拿学， 2011， 博士

【摘要】 背景：轻度认知功能障碍(MCI)是一种发生在老年人群中的综合征,介于正常老龄及轻度痴呆之间的具有疾病特征的一种临床状态。MCI患者临床表现为与年龄和受教育程度无关的记忆力减退、工作能力和效率下降、注意力集中减退、学习新事物能力下降,但有相对正常的日常生活能力和认知能力,未达到临床诊断为痴呆的标准。处于这种状态的个体存在超出其年龄所允许的记忆障碍,虽然达不到痴呆的诊断标准,但是MCI往往代表老年性痴呆(AD)的早期阶段。随着社会的发展,世界老龄化问题日益突出,早期发现、早期诊断、早期干预轻度认知障碍有着极其重要的社会、经济和医学价值。针灸在防治老年病方面有独特的疗效,但其作用中枢机制和机理还缺乏影像学依据。目的：本课题拟运用3.0T功能磁共振成像技术(fMRI),以不同脑区的血氧代谢变化为指标,研究MCI患者太溪穴、人中穴和非穴的脑功能成像特点,经穴的相对特异性；从不同脑区功能变化来探讨MCI患者针刺太溪穴、人中穴的脑功能效应中枢机制。旨在解决MCI患者针刺太溪穴、人中穴特异性脑功能界定、探索经穴的脑功能成像特点和规律。从脑功能方面界定经穴和非穴,并进一步进行经穴特异性一脑相关的信息的汇集,为针刺治疗MCI提供影像学依据。方法：利用脑功能磁共振成像(functional magnetic resonance imaging, fMRI)纳入MCI被试36例,其中男性10例,女性26例,年龄在56-72岁；正常被试(对照组)12例,男性4例,女性8例,年龄在55-76(60.6±5.8)岁。MCI被试随机分为太溪穴针刺组、非穴针刺组、人中穴针刺组,均为12例。36例MCI被试均符合该症诊断标准,为右利手,近一个月内未使用任何可能影响认知功能的药物,无功能磁共振扫描禁忌症者。选穴：选取人中穴、右侧太溪穴和非穴。非穴选在太溪与跟腱连线的中点。常规消毒,选0.35×25mm银质针1根刺入所取穴位,垂直进针15mm(人中穴为向上斜刺),采用均匀提插捻转行针法,捻转角度180°,提插幅度在上下1mm,频率均为60次／分钟。为避免针刺后效应的影响,本次实验采用单组块设计(single block design),即静息期(无任何刺激)、针刺期(进行针刺并均匀提插捻转)以及针刺后效应期。fMRI扫描观察不同处理状态下的脑功能成像特点。应用Matlab(Math Works Inc., Natick, MA)和统计参数图(SPM2)软件进行fMRI的数据处理。首先将功能图像序列进行空间配准,并标准化到Montreal Neurological Institute (MNI)标准模板,然后利用半高宽(FWHM)为8mm×8mm×8mm的三维高斯函数对标准化后的数据做空间平滑。根据血液动力学响应函数hrf进行固定效应分析,然后进行双样本t检验,检验被试者的针刺后效应期与静息期的差异,以P<0.001, uncorrected, K≥10voxels的像素标准构成统计参数图,该图即为实验任务激活的脑区,最后将激活区的坐标转换到Talairach空间。结果：1、MCI患者针刺前较正常人血氧代谢降低的脑区为左侧额上回(BA6)、左侧边缘叶扣带回(BA24)、右侧颞上回(BA38)；2、针刺太溪穴激活右侧边缘叶扣带回(BA24)、双侧额内侧回(BA6)、左侧中央后回BA3；3、MCI针刺非穴主要激活左侧顶下小叶(BA40)、左侧中央后回(BA2)、左小脑前叶蚓部。4、MCI针刺人中穴主要激活右侧额下回(BA45,13)、右侧额中回(BA47,10,6)、右侧颞中回(BA21),其次激活双侧额上回(BA10)、右侧中央前回(BA6,4)、左侧颞上回(BA38)、左侧颞中回(BA38)、左侧颞下回(BA20)、右侧颞中回(BA21)左侧前扣带回(BA24)。结论：本研究结果显示,针刺前MCI患者组与正常组比较,左侧额上回(BA6)、左侧边缘叶扣带回(BA24)和右侧颞上回(BA38)血氧代谢降低,即被抑制状态,证明了作为AD的前期病变,在轻度认知障碍性疾病中,额叶、颞叶常有不同程度的病变。针刺太溪穴、人中穴能特异性提高额顶叶、颞叶和边缘叶的血氧代谢。针刺太溪穴和人中穴靶向性激活了MCI患者病变脑区,且对于相关脑区具有整体性调节效应。额顶叶与认知功能相关性大,也就是与中医的“神”有关。中医认为,肾为先天之本,肾藏精,精化气,气生神,三者之间是相互滋生、相互助长的。此外,中医理论认为“病变在脑,首取督脉”。太溪和人中这种激活,是与本经的循行、本经属络脏腑以及本经络与他经经络、脏腑联系密切相关。本研究发现针刺太溪穴与针刺非穴对比,能较为特异地激活在认知、记忆、感情密切相关的脑区。非穴只激活主管协调功能的运用中枢BA40和皮质一般感觉区BA6。针刺太溪穴有明显指引性或规律性,而针刺非穴却没有明显指引性或规律性,这在一定程度上印证了“经穴特异性-脑相关学说”。更多还原

【Abstract】 Background:Mild cognitive impairment is a kind of happened in the elderly between normal ageing and integratedly, with disease characteristics between dementia, a clinical condition. MCI patients’clinical manifestations of education degree with age and be independent of memory loss, working ability and efficiency descend, concentration drops, reduced ability to learn new things. But they have relatively normal daily living skills and cognitive ability and would not meet the standard for clinical diagnosis of dementia. In this state of patients exist beyond its age allowed by memory disorders, although cannot reach the diagnosis of dementia(AD) standards, but it often represent senile dementia early phase. Early detection, early diagnosis, early intervention to the mild cognitive impairment can prevent or delay the oceurrence and progress of dementia, which is of significance and an extremely important social, economic and medical value. Acupuncture in control this elderly patient is the special effect, but its central mechanism is lack of imaging basis.Objective:To study brain imaging characteristics and the relative specificity supersession of needling Renzhong(DU 26)、Taixi(KI 3) and nonpoint by fMRI, and blood oxygen metabolism changes in brain areas for indexes. From different brain regions to explore the brain function in effect central mechanism from function change in patients with MCI needling Taixi (KI 3) and Renzhong(DU 26). From brain function definition to provide imaging basis acupuncture treatment of MCI.Methods:36 patients with MCI and 12 normal aging people were enrolled in this research.36 patients, including male 10 cases, female 26 cases, age 56 to 72 years old.12 normal cases, including male 4 cases, female 8 cases, age 55 to 76 years old. MCI patients were randomly divided into Taixi (KI 3) group, nonpoint group and Renzhong(DU 26) group and they were all 12 cases.36 patients with MCI all accord with the diagnostic criteria and right handed. Nearly a month not taking any affected cognitive function drugs, no functional magnetic resonance imaging (mri) scan the contraindication disease.Choose acupuncture point:select the right Taixi(KI 3) and Renzhong(DU 26). The nonpoint is chosen in the midpoint of attachment between Taixi (KI 3) and achilles tendon.Regular disinfection the skin, needle 15mm in the apoint by 0.35×25mm silver needle. Twisting 180°,turn amplitude frequency 60 times/min, lift inserted in fluctuation 1 mm amplitude. A block design including three blocks, resting state, rotating state and persistent after effect state.fMRI scanning takes approximately condition, and observe different treatment of brain function imaging characteristics. fMRI data were processing by the application of Matlab and SPM2 software. First realigned and normalized to Montreal Neurological Institute, then use half tall width (FWHM) 8mm x 8mm x 8mm for 3d gaussian function after standardization of data to make space smooth. According to hemodynamic response function hrf fixed effect analysis, then double sample t-test, inspection the difference between After effect of acupuncture and resting phase. Finally brain area activated will be transformed to the Talairach space.Results:1、The brain areas which blood oxygen for metabolic reduced including the left superior frontal gyrus (BA6)、left cingulate gyrus (BA24)、right superior temporal gyrus (BA38) before needling in MCI patients.2、The brain areas including the right cingulate gyrus (BA24)、medial frontal gyrus(BA6)、left postcentral gyrus (BA3) were activated when needling Taixi(KI 3) in MCI patients.3、The brain areas including the left inferior parietal lobule (BA40)、left postcentral gyrus (BA2)、left cerebellum anterior lobe culmen were activated when needling nonpoint in MCI patients.4、The brain areas including the right inferior frontal gyrus (BA45, 13)、right middle frontal gyrus(BA47,10,6)、right middle temporal gyrus (BA21), superior frontal gyrus (BA10)、right precentral gyrus (BA6, 4)、left superior temporal gyrus (BA38)、left middle temporal gyrus (BA38)、left Inferior temporal gyrus (BA20)、right middle temporal gyrus (BA21)、left anterior cingulate (BA24) were activated when needling Renzhong(DU 26) in MCI patients.Conclusion:The results suggest that MCI group of patients with normal before with acupuncture group compared leftsuperior frontal gyrus(BA6), left cingulate gyrus (BA24) and rightsuperior temporal gyrus (BA38) reduces blood oxygen metabolism, i. e. restrained by state. It proved that the AD prophase lesions, in mild cognitive barrier disease, the frontal and temporal lobes often have different degrees of lesions.Needle Taixi (KI 3) and Renzhong(DU 26) would specificity that enhance their blood oxygen metabolism. Needle Taixi(KI 3) and Renzhong(DU 26) target-based activates the lesions brain regions of MCI, and it regarding related brain regions have integrity adjustment effect. Frontal lobe and Parietal lobe have great correlation with cognitive function, which means they have great correlation with mind and brain. Frontal lobe and Parietal lobe have great correlation with cognitive function, which means they have great correlation with mind and brain. In addition, Chinese medicine theory is that brain sick when should be first treatment du meridian. The activation reaction of Taixi (KI 3) and Renzhong(DU 26), is with the meridian line and its contact Morrison is closely related to the viscera.This study found that needle Taixi(KI 3) and nonpoint contrast, can activate brain regions that more specific in cognition, emotion and memory. Using central BA40 and cortical generally feel area BA6 when needling nonpoint in MCI patients.Needle Taixi(KI 3) would activate bilateral brain and deep brain, and needle nonpoint only activate left brain. Needle Taixi (KI 3) has obvious regularity, but nonpoint hasn’t. This, to a certain extent, proved "meridians specificity-brain related theory".更多还原