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基于fMRI的得气对脑功能活动影响的系统综述

【作者】 张壮

【导师】 朱江;

【作者基本信息】 北京中医药大学 , 针灸推拿学, 2018, 硕士

【摘要】 得气,首出于《黄帝内经》,“刺之要,气至而有效。效之信,若风之吹云,明乎若见苍天。”《难经》对得气也多有论述,甚至有“不得气,是谓十死不治也”的记述。可以见得,古代医家认为,诱发得气是针刺取得临床疗效的关键。《灵枢·小针解》曰:“空中之机,清净以微者,针以得气,密意守气勿失也。”说明得气是针刺过程中的重要环节,且不易把握。“气至而去之者,言补泻气调而去之也。”“春夏温,必致一阴者,初下针,沉之至肾肝之部,得气,引持之阴也。秋冬寒,必致一阳者,初内针,浅而浮至心肺之部,得气,推内之阳也。”在古代医籍论述中,得气是针刺过程中经气汇聚的现象,还有针刺得气后通过施行补泻手法以达到气机调和、阴阳调和状态的含义。现代对得气的定义较为统一,普遍认为得气是指“毫针刺入腧穴一定深度后,施以提插或捻转等行针手法,使针刺部位获得经气感应。”得气后,患者的针刺部位有酸胀、麻重等得气感,同时,医者亦能体会到针下沉紧、涩滞或针体颤动等反应。得气是针刺治疗取得临床疗效的关键环节之一,亦是近年来针刺研究的热点。近年来国内外研究者进行了大量的基于中枢脑活动的得气客观化研究,其中功能性磁共振成像(fMRI)技术因具有无创、无辐射、空间分辨率高等优势,在得气的客观化研究中应用最为广泛。基于fMRI的得气中枢研究有助于探索得气的本质及其作用机制,有利于得气的临床应用及其研究的进一步发展。为了全面和深入地了解基于fMRI的得气客观化研究进展,本研究拟进行文献综述及系统综述以对其研究成果进行系统性的总结。研究一:背景:笔者对近十年来的得气客观化研究,尤其是得气的fMRI研究进行了总结和分析。还对针刺效应与中枢反应的相关性进行了理论探讨,分析了对针刺中枢效应的探索在针刺研究中的重要作用。初步认为进行基于fMRI技术的得气对脑功能活动影响的系统评价有其必要性和可行性。目的:通过比较针刺后得气状态与不得气状态下的脑功能活动差异,评价针刺经穴后得气对脑功能活动的影响。方法:检索国内外10个医学文献数据库,包括中国国家知识基础设施工程数据库(CNKI)、万方数据库、维普数据库(VIP)、中国生物医学文献数据库(CBM)、MEDLINE医学文献数据库、Cochrane Library CENTRAL、荷兰医学文摘数据库(EMBASE)、护理学及医疗相关文献累计索引数据库(CINAHL PLUS)、精神医学信息数据库(PsycINFO)、联合补充医学文献数据库(AMED);以及5个临床试验注册平台,包括美国国立医学图书馆临床试验注册中心、世界卫生组织国际临床试验注册平台、英国国际标准随机对照试验注册库、澳大利亚-新西兰临床试验注册中心、中国临床试验注册中心。检索时间从建库至2018年1月。同时检索灰色文献网站OpenGrey并对纳入研究的参考文献进行手工检索。系统收集以fMRI为观察指标,比较针刺经穴后得气与不得气状态下脑功能活动差异的临床试验文献。结局指标要求包含激活脑区的MNI或Talairach空间坐标,采用SDM(Seed-based d Mapping)软件进行体素meta分析。方案注册号:PROSPERO:CRD42016043209。结果:共检索到文献4612篇,4篇文献(共79名受试者)符合纳入标准。对其中4项研究进行体素meta分析后,结果显示针刺得气较不得气在右缘上回、左值网络和左侧中央后回等脑区的激活更为显著。结论:初步认为针刺经穴后得气与不得气状态下脑功能活动不同,得气状态下激活的脑区更多,激活的程度更强。但由于研究间的异质性较大,因此上述结论有待进一步研究证实。研究二背景:基于第一项系统综述的经验和局限性,拟进行一项针对某一特定经穴得气后的脑功能活动改变的系统综述,对得气在中枢层面上的影响进行更为深入的探讨。由于足三里是针刺的临床和研究中应用较为普遍的穴位,对足三里得气的fMRI研究文献数量较多,因此第二项系统综述选择足三里作为研究经穴,系统评价针刺足三里得气后相较于静息状态的脑功能活动变化。目的:通过比较针刺足三里得气后较静息状态的脑功能活动差异,评价针刺足三里后得气对脑功能活动的影响。方法:检索数据库同研究一,时间从建库至2018年1月。系统收集以fMRI为观察指标,比较针刺足三里得气对脑功能活动影响的临床试验文献。结局指标要求包含激活脑区的MNI或Talairach空间坐标,采用SDM软件进行体素meta分析。结果:最终纳入10篇文献,共185名受试者。其中6篇为中文文献,4篇为英文文献。均值分析的结果显示针刺足三里后有5个脑区的活动较静息状态更为活跃,这5个脑区分别是右额下回,眶部,右中值扣带/扣带旁回,右缘上回和右脑桥。活动较静息状态有所抑制的脑区有右枕中回,中央旁小叶,右小脑脚左枕中回以及左舌状回。Jackknife敏感性分析显示结果较为稳定。结论:初步认为针刺足三里得气后,较静息状态脑区的活动有显著改变。针刺足三里得气后激活/负激活的区域主要集中在与躯体感觉与运动、平衡、情绪调节、记忆等方面相关的脑区,可能与足三里穴的功能主治有相关性。但是目前的结果在稳定性上仍值得商榷,还需进一步的研究证实。

【Abstract】 Background:Deqi is one of the key points in the clinical efficacy of acupuncture treatment and also a hot spot in acupuncture research in recent years.The importance of deqi and it’s characteristic that being difficult to grasp require us to explore the mechanism of deqi with relatively objective indicators.Researchers at home and abroad have carried out a large number of objectified studies of deqi based on central brain activity.Among them,fMRI has been applied in the objective study of deqi most widely because of its advantages of non-invasive,non-radiation and high spatial resolution.In order to systematically summarize the research progress of deqi based on fMRI,we present a systematic review.Using the method of voxel meta-analysis,we evaluated the effect of deqi on brain function effects and summed up the activited/deactivated pattern of brain function effects induced by deqi.Study 1Background:The objective research of deqi in the past ten years,especially the fMRI study of deqi,is summarized and analyzed.The relationship between the acupuncture effect and the central reaction was also discussed theoretically,we think exploring the central effect of acupuncture is important for acupuncture research.It is preliminarily considered that it is necessary and feasible to carry out a systematic review of the effects of deqi on brain functional activities based on fMRI technology.Objective:To evaluate the influence of deqi on brain function effects after acupuncture compared with non-deqi state after acupuncture.Method:We searched the following 10 electronic databases:CNKI,CBM,VIP,the Wanfang Database,MEDLINE,CENTRAL,CINAHL,AMED,Embase,PsycINFO and 5 clinical trial registration platform.The time is from building of the library to January 2018.The trials comparing different brain function effects in deqi group with non-deqi group that employed fMRI technology were collected.The SDM(Seed-based d Mapping)software will be used for voxel meta analysis when the outcome contains MNI or Talairach space coordinates of the activated/deactivated brain regions.Results:4612 articles wereretrieved,andfour trials involving 79 subjects were included.Voxel meta analysis was conducted using SDM software with four studies involved,the result shows that there are more activated brain regions in Right supramarginal gyrus,Left median network,Left postcentral gyrus,etc in deqi state than non-deqi state.However,due to the large heterogeneity between the trials,the activated brain regions shown in the results were not representative.Conclusion:The initial point of view is that brain function effects is different between deqi and non-deqi state.There do have more activation brian areas in the deqi condition compared to non-deqi condition,and the degree is stronger.The specific activated brain regions after acupuncture needs further confirmed by more high quality studies.This review protocol is registered in PROSPERO:CRD42016043209.Study 2Background:Based on the experience and limitations of the first system review,it is planned to carry out the second systematic review of the changes in the brain functional activity owing to deqi after acupuncturing a particular acupoint,and the effect of deqiin the central level will be further discussed.As Zusanli is a common acupoint in clinical and research of acupuncture,and there are many deqi studies based on fMRIon Zusanli.Therefore,the second systematic review selected Zusanli as the study point to evaluate the functional activity changes of brain after deqi than in the relative resting state at Zusanli.Objective:To evaluate the influence of deqi after acupuncturing at Zusanli on brain function effects compared with resting state.Methods:We searched the following 10 electronic databases and 5 clinical trial registration platform.The time is from building of the library to January 2018.The clinical trial literatures that used fMRI as the observation index and compared the effects of deqi on brain function activity were collected systematically.The outcome index should include the MNI or Talairach coordinates of the activated/deactivated brain regions.The voxel meta-analysis is carried out with the SDM(Seed-based d Mapping)software.Results:10 literatures involving 185 subjects were included.Six of the literatures are in Chinese and four are in English.Mean analysis results show that five brain regions after acupuncture were more active:right inferior frontal gyrus、orbital part(BA 47),right median cingulate/paracingulate gyri(BA 24),left rolandic operculum(BA 48),right supramarginal gyrus(BA 40)and rght pons.There were 5 brain regions deactivated than the resting state after deqi:right middle occipital gyrus(BA 18),left paracentral lobule,right cerebellum、crus I(BA 19),left middle occipital gyrus(BA 19)and left lingual gyrus(BA 27).Jackknife sensitivity analysis shows that the results are stable.Conclusion:The authorpreliminarily consider that there is a significant difference in the activity of the brain after deqi compared to resting state.The activated/deactivated brain areas were mainly concentrated on the brain regions that relevant to somatosensory and movement,balance,emotion regulation,memory and so on,whichmay have correlations with the acupoint function of Zusanli.

【关键词】 得气fMRI足三里系统评价
【Key words】 AcupunctureDeqiZusanlifMRISystematic Review
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