【作者】 陈彦文；

【导师】 柯美云；

【作者基本信息】 北京协和医学院 ， 临床医学， 2012， 博士

【摘要】 背景和目的功能性消化不良(FD)的发病机制尚不明确,不同亚型之间可能存在病理生理基础的异质性。内脏高敏感是FD发病的重要机制之一,有研究提示上腹痛综合征(EPS)可能与之更为相关。中枢是内脏感觉处理的中心,FD在内脏疼痛神经网络的活动性与健康人存在差异。本研究试图利用血氧水平依赖性功能性磁共振成像技术(BOLD-fMRI)观察FD各亚型脑区活动的差异,并探讨可能的影响因素。对象和方法包括10例EPS、7例餐后不适综合征(PDS)和7例混合型在内的24例FD患者以及10例健康人(HS)纳入研究。对受试者近端胃施以两种温度(37℃和4℃)的水负荷刺激,观察各组在静息态与不同温度水负荷刺激下脑区活动的差异。对每例FD患者评估消化不良症状、焦虑抑郁、社会支持、患病行为、胃肠动力功能等情况,并分析上述指标与脑区活动的相关性。结果(1)FD患者静息态脑区活动与HS在边缘叶(海马旁回)、苍白球、前额皮质、小脑、脑桥等区域存在显著性差异(P<0.05)。分别观察FD各亚型时,相比PDS或混合型,EPS与HS的差异性更大,表现为边缘系统(包括扣带回、海马旁回、颞极)、前额皮质更广泛的差异性,并且累及右侧岛叶、左侧颞叶、右侧枕叶。(2)FD患者37℃水负荷任务相关的脑区激活在左侧边缘叶(中扣带回、背侧后扣带回)、左侧颞中回、颞下回等脑区低于HS(P<0.05),而在左侧小脑及蚓部、双侧枕叶以及右侧次级躯体感觉皮质(SⅡ)等脑区高于HS(P<0.05)。相比PDS或混合型,EPS患者与HS差异更明显。(3)4℃水温刺激下,HS的双侧边缘系统(前中后扣带回、岛叶、颞极)、前额皮质、脑桥均有参与激活或负激活(P<0.05)。与37℃相比,前扣带回、丘脑的激活在EPS对冷刺激的反应中更强,并且这种激活强度的差异性比HS中更明显。(4)FD患者的症状评分与前扣带回、前额皮质、海马旁回、颞极、顶上小叶等区域存在显著相关性(P<0.01)。右侧海马旁回、右侧颞下回、右侧额上回、左侧角回、左侧额下回三角区、右侧小脑脚是与各社会心理量表评分相关性最高的几个区域(R>0.684,P<0.01)。胃肠动力功能方面,左侧颞下回、右侧额中回、左侧额上回分别与最大灌注量、近端胃内压力变化、近端胃顺应性有良好的相关性(R值分别为0.910,-0.880,-0.844,P<0.01)。结论FD的静息态和不同温度水负荷刺激下的脑区活动与HS均有明显差异,这些差异受到症状严重程度、社会心理因素、胃肠动力功能等诸多因素的影响。EPS与HS脑区活动的差异较PDS更明显,这可能提示中枢神经系统疼痛处理的异常是EPS发病的主要机制。更多还原

【Abstract】 Background and ObjectivesThe pathogenic mechanism of functional dyspepsia (FD) has not been elucidated well. Heterogeneities in pathophysiological basis may exist among different subtypes. Visceral hypersensitivity is one the most important mechanisms of FD pathogenesis, which is considered to have closer relationship with epigastric pain syndrome (EPS) by some studies. Central nervous system is the center for visceral sensation processing. The regional brain activity of visceral pain neuromatrix has been found different between FD patients and healthy people. This study aims to observe the regional brain activity difference among subtypes of FD, with the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI), and to look into some possible influential factors.Patients and MethodsTwenty-four FD patients, including10EPS,7post-prandial distress (PDS) and7mixed type patients, and10healthy subjects (HS) were enrolled. Every subject was given proximal gastric water load test with pure water of2temperatures (37degree and4degree centigrade), whose regional brain activities during resting state and under water load of different temperatures were observed and compared at the group level. Every FD patient was evaluated on dyspepsia symptoms, anxiety and depression state, social support, illness behavior and gastric motility functions. The correlations between regional brain activity and those indices were then analyzed.Results(1) Differences of resting state regional brain activities between FD and HS were found in limbic lobe (parahippocampal gyri), pallidum, prefrontal cortex, cerebella and pons (P<0.05). EPS showed more significant difference from HS, compared to PDS or mixed type, on limbic systems (including cingulate cortices, parahippocampal gyri, temporal pole) and prefrontal cortex, and involved right insula, left temporal lobe and right occipital lobe as activity difference areas.(2) Comparing the37℃water load task related regional brain activations between FD and HS showed the following difference:lower activations in left limbic lobe (middle cingulate cortex, dorsal posterior cingulate cortex), left middle and inferior temporal gyri (P<0.05), while higher activations in left cerebelllum and vermis, bilateral occipital lobes and right secondary somatosensory cortex (SH)(P<0.05). EPS showed greater difference from HS, compared to PDS or mixed type.(3) Under the4℃water load stimulation, HS showed (de)activations in bilateral limbic system (anterior, middle and posterior cingulate cortices, insula and temporal poles), prefrontal cortices and pons (P<0.05). EPS showed greater response in anterior cingulate cortex and thalamus activation to cold stimulus than37℃water, and this feature of activation difference was more obvious than HS.(4) The dyspepsia symptom score of FD had significant correlations with anterior cingulate cortex, prefrontal cortex, parahippocampal gyrus, temporal pole and superior parietal lobule (P<0.01). The regions with top correlations with various psychosocial scales were found to be right parahippocampal gyrus, inferior temporal gyrus, superior frontal gyrus, cerebellar crus, and left angular gyrus and inferior frontal gyrus (.R>0.684, P<0.01). Concerning the gastric motility functions, left inferior temporal gyrus, right middle frontal gyrus and left superior frontal gyrus showed good correlations with maximal perfusion volume, proximal intragastric pressure change and proximal gastric compliance, respectively.ConclusionsThe regional brain activity of FD is significantly different from HS, both during the resting state and under water perfusion stimulus of different temperatures. The difference could be influenced by symptom severity, psychosocial factors, and gastrointestinal motility. When comparing FD subtypes with HS, EPS showed greater difference than PDS, which may indicates that the abnormality of pain processing by central nervous system is the main pathogenic mechanism of EPS.更多还原