【作者】 曾芳；

【导师】 梁繁荣；

【作者基本信息】 成都中医药大学 ， 针灸推拿学， 2010， 博士

【摘要】 目的：评价循经取穴治疗功能性消化不良(Functional Dyspepsia, FD)的临床疗效,探讨循经取穴治疗FD的中枢神经响应特征,为循经取穴治疗FD的临床运用提供科学的试验依据。方法：1、采用多中心、随机、对照的临床研究方法,通过中央随机系统将符合纳入标准的354例FD患者随机分为A组(循经取穴组)、B组(非循经取穴组)和C组(非经非穴组)。按照不同的取穴方案,各组受试者每天接受1次电针治疗,共治疗20次。以尼平消化不良量表(Nepean Dyspepsia Index, NDI)生活质量评分表和消化不良症状积分为疗效评价指标,分别于治疗2周、治疗结束、治疗结束后4周随访和12周随访4个时间点评价不同取穴针刺治疗FD的临床疗效。2、从临床研究各组中各纳入10例符合脑功能成像研究要求的FD患者,以正电子发射计算机断层扫描(Positron Emission Tomography-Computed Tomography, PET-CT)技术为研究手段,通过对比FD患者与健康受试者静息状态下脑葡萄糖代谢的差异,对比病情较轻FD患者与病情较重FD患者静息状态下脑葡萄糖代谢的差异,分析FD患者各个脑区葡萄糖代谢的变化与病情的相关性,探讨FD患者静息状态下脑功能活动的特征,筛选与FD病情相关的重点脑区；再通过对比不同取穴针刺对FD患者脑功能和FD病情相关重点脑区的影响,探讨循经取穴针刺治疗FD的中枢响应特征。结果：1、循经取穴针刺治疗FD的临床疗效评价结果(1)3组受试者基线一致,具有可比性。(2)NDI量表评价结果显示：3组FD患者针刺治疗后NDI量表评分与治疗前相比均显著降低(p<0.01)。但只有A组在治疗2周、治疗结束、治疗结束后4周随访和12周随访4个时间点的NDI量表评分改善值均具有临床意义(改善值≥10分)；A组在4个疗效评价时间点的NDI量表评分改善值与B组、C组相应时间点NDI量表评分改善值相比均有统计学差异(p<0.01)。(3)消化不良症状积分结果显示：A组针刺治疗后4个主症症状积分与治疗前相比均显著降低(p<0.05)。A组在4个时间点的餐后饱胀不适症状积分改善值、在3个时间点(除12周随访)的早饱症状积分改善值、在2个时间点(除2次随访)的上腹痛症状积分改善值与B组、C组相应时间点的改善值相比,均有统计学差异(p<0.05)。(4)治疗结束时,A组总有效率(FAS集：92.27%,PP集：97.27%)与B组、C组比较均有统计学差异(p<0.01)。2、FD患者静息态脑功能活动特征研究结果(1)健康受试者与FD患者静息状态下脑葡萄糖代谢的差异：与健康受试者相比,FD患者以边缘系统为主的多个脑区葡萄糖代谢显著增高,包括双侧脑岛(Brodmman area 13, BA13),前扣带回(Anterior Cingulate Cortex, ACC) (BA24, BA32)、中扣带回(Middle Cingulate Cortex,MCC)(BA23,BA32)、后扣带回(Posterior Cingulate Cortex,PCC) (BA30)、海马旁回(BA35)、尾状核、屏状核、豆状核、海马、下丘脑、杏仁核和小脑,双侧额叶(BA47、BA8、BA9、BA10、BA4、BA3、BA1l),双侧枕叶(BA23、BA37、BA19),双侧顶叶(BA43、BA7、BA40、BA39、和双侧颞叶(BA20、BA21、BA38、BA41)(p<0.001)；未见葡萄糖代谢降低区域。(2)与FD病情密切相关的重点脑区：FD患者双侧丘脑、ACC、MCC、脑岛和小脑葡萄糖代谢的异常增高与NDI量表评分呈极显著负相关(p<0.01),与病情呈显著正相关；与病情较轻FD患者相比,病情较重FD患者双侧丘脑、ACC、MCC、脑岛和小脑的葡萄糖代谢显著增高(p<0.005)3、循经取穴针刺对FD患者脑功能的影响研究结果(1)各组针刺对FD患者脑功能活动的影响：A组针刺后FD患者边缘系统-大脑各个脑区异常增高的葡萄糖代谢全面降低,包括：双侧脑岛(BA13)、ACC (BA24、BA32)、MCC (BA31、BA32)、PCC (BA29、BA30)、丘脑、海马旁回(BA35、BA19)、尾状核、屏状核、豆状核、海马、下丘脑、杏仁核和小脑,双侧额叶(BA6、BA8、BA9、BA45、BA47、BA11、BA3),双侧枕叶(BA19),双侧顶叶(BA7、BA40、BA23、BA39),双侧颞叶(BA37、BA19、BA21、BA22) (p <0.005); B组针刺后FD患者左侧ACC (BA24)、PCC (BA31)、豆状核、海马、梭状回(BA 37)和颞下回(BA20),双侧丘脑腹外侧核和小脑扁桃体异常增高的葡萄糖代谢显著降低(p<0.005)；C组针刺后FD患者右侧MCC(BA23),左侧额中回(BA6),双侧PCC(BA23)、丘脑腹外侧核、顶叶楔前叶(BA30)、枕叶舌回(BA17)、中央前回(BA6)和小脑山坡异常增高的葡萄糖代谢显著降低(p<0.005)。(2)各组针刺对FD病情相关重点脑区功能活动的影响：A组针刺对FD病情相关的所有重点脑区——双侧脑岛、ACC、丘脑、MCC和小脑的异常激活均有显著的抑制作用(p<0.05)；B组针刺只对左侧ACC异常激活有显著的抑制作用(p<0.05)；C组只对右侧MCC和右侧丘脑的异常激活有显著的抑制作用(p<0.05)。结论：1、循经取穴针刺治疗FD疗效优于非循经取穴和非经非穴针刺,循经取穴治疗FD安全、有效。2、FD患者与健康受试者相比静息状态下脑功能活动存在显著差异。边缘系统-大脑葡萄糖代谢的整体升高可能是FD患者静息态脑功能活动的主要特征。ACC、脑岛、丘脑、MCC和小脑可能是与FD病情密切相关的重点脑区。3、循经取穴针刺可全面降低FD患者边缘系统-大脑各脑区异常增高的葡萄糖代谢,显著调节与FD病情相关的各个重点脑区的功能活动。与非循经取穴和非经非穴针刺相比,循经取穴针刺治疗FD的中枢响应以边缘系统-大脑的协同整合及对FD病情相关重点脑区的靶向性调节为特征。更多还原

【Abstract】 Aim:To evaluate the clinical efficacy and explore the central mechanism of puncturing at the acupoints on the involved meridian for Functional Dyspepsia patients.Methods:1. Multi-center, randomized and controlled trial was designed.354 patients who matched the inclusion criteria were randomly divided into 3 groups. Each group was administered puncturing at different ponints:Group A:acupoints on the involved meridian (ST34, ST36, ST40 and ST42); Group B:acupoints on the non-involved meridian (GB34, GB36, GB37and GB40), and Group C at four non-acupoints. Electroacupuncture with HAN’s acupoint nerve stimulator was used at these points respectively once per day and totally for 20 days. The Nepean Dyspepsia Index (NDI) and Dyspepsic Symptom Score were used to evaluate the clinical efficacy after 10 days’ and 20 days’treatment,4 weeks follow-up and 12 weeks follow-up.2. Brain fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed on 32 FD patients and 12 healthy subjects (HS) in resting state. The characteristics of resting-brain activities in FD patients were obtained by comparing the cerebral glycometabolisms in FD patients with those in HS, the cerebral glycometabolisms in the milder FD patients and those in the relatively severer FD patients using Statistical Parametric Mapping software (SPM5.0), and analyzing the correlation between the changes in cerebral glycometabolism and the NDI scores of FD patients.18F-FDG PET-CT was performed on FD patients in Group A, B and C after 20 days’treatment. The characteristics of cerebral responses to puncturing at the acupoints on the involved meridian were obtained by comparing the changes in cerebral glycometabolism of the FD patients in Group A after acupuncture treatment with those of the FD patients in Group B and Group C.Results:1. The clinical efficacy of puncturing at the acupoints on the involved meridian1) The baselines of the three groups showed no statistical differences (p>0.05) 2) Although the NDI scores for Group A, Group B and Group C were all significantly improved after the treatment (p<0.01), only the improvements in Group A at all four assessment times were clinically significant, with an increase of more than 10 points on the NDI total scores. The changes in the NDI scores of Group A very significantly differed from those of Group B and Group C at all four assessment times (p＜0.01)3) The Dyspepsic Symptom Scoreson the four main symptoms for Group A were all significantly improved after the treatment (p<0.05). The improvements on postprandial fullness, early satiation and pigastric pain in Group A were significant better than those in Group B and Group C (p<0.05)4) There was significant difference between the three groups in the overall efficacy at the end of treatment (p<0.01).2. The characters of resting-brain activities in FD patients1) The difference in cerebrl activities between FD patients and HS:Compared to the HS, the FD patients showed increased glycometabolism in Insula (Brodmman area 13, BA13), Cingulate Cortex (BA24.31,32,30), Parahippocampal Gyrus (BA35), Caudate, Claustrum, Lentiform Nucleus, Thalamus, Hippocampus, Hypothalamus, Amygdala, Cerebellum, Frontal Cortex (BA3,4,8,9,10,11,47), Temporal Cortex (BA20,21,39,41), Parietal Lobe (BA7,40,43.39) and Occipital Lobe (BA23,37.19) (p<0.001);2) The key regions which might be closely relate to the pathology of FD:the activations in Middle Cingulate Cortex (MCC), Cerebellum, Thalamus, Anterior Cingulate Cortex (ACC) and Insula showed a very significant negative correlation with the NDI scores (p<0.01):the activations in MCC, Thalamus, ACC, Insula and cerebullum of the relatively severer patients significantly differ from those of the milder patients (p<0.005).3. The influence of different acupuncture methods on the resting-brain activities in FD patients1) The abnormally high cerebral glycometabolism of FD patients in Group A were all decreased significently after acupuncture treatment at Insula (BA 13), Cingulate Cortex (BA 24,31,32,29), Parahippocampal Gyrus (BA35), Caudate, Claustrum, Lentiform Nucleus, Thalamus, Hippocampus, Hypothalamus, Amygdala, Cerebellum, Frontal Lobe (BA 3,6,8,9,11,45,47), Temporal Lobe (BA19,21,22,37), Parietal Lobe (BA7,40,23,.39) and Occipital Lobe (BA 19) (p<0.005); The abonormally high cerebral glycometabolism of FD patients in Group B were slightly decreased after acupuncture treatment at left ACC (BA24), Posterior Cingulate Cortex (PCC, BA31), Lentiform Nucleus, Hippocampus Fusiform Gyrus (BA 37) and Inferior Temporal Gyrus (BA20), bilateral Thalamus and Cerebellum Tonsil (p<0.005); The abonormally increased cerebral glycometabolism of FD patients were partly decreased after acupuncture treatment of Group B including right MCC (BA23), left Middle Frontal Gyrus (BA6), bilateral PCC (BA23), Thalamus, Precuneus (BA30), Lingual Gyrus (BA17), Precentral Gyrus (BA6) and Cerebellum (p<0.005)2) All the key regions which might closely related to the pathology of FD including MCC, Cerebellum, Thalamus, ACC and Insula all showed significantly signal decrease after acupuncture treatment of Group A (p<0.05); only left ACC showed a signal decrease after acupuncture treatment of Group B (p<0.05); only right MCC and Thalamus showed signal decrease after acupuncture treatment of Group C (p<0.05)Conclusions:1. The clinical efficacy of puncturing are better at the acupoints on the involved meridian (Group A) for FD than at the acupoints on the non-involved meridian (Group B) and at non-acupoints (Group C).2. There are significant differences in resting brain activities between FD patients and HS. The general hyperactivities in cerebral-limbic system should be the main characteristic of the brain activities in FD patients. ACC, Insula, Thalamus, Cerebellum and MCC might be the core regions that closely relate to the pathogenesis of FD.3. The cerebral response to puncture at the acupoints on the involved meridian for FD might be characterized by inducing the co-operation of cerebrum and limbic system and regulating the functions of the FD-related key regions.更多还原