脑-肠互动在肠易激综合征发病中的作用

肠易激综合征(IBS)发病机制尚未完全阐明.目前研究认为,其发病机制与胃肠动力异常、内脏高敏感性、肠道感染、脑-肠互动、脑肠肽和受体以及社会心理因素有关,而脑-肠互动在IBS发病中的作用引起研究者的普遍关注,IBS上述的发病因素均可整合到脑-肠互动框架中进行阐述,脑-肠互动是研究IBS发病机制的切入点.本文从脑-肠轴及脑-肠互动,IBS发病因素与脑-肠互动以及临床治疗研究3个方面阐述脑-肠互动在IBS发病中的重要作用,以揭示脑-肠互动病理生理实质.     

迷走神经参与肠易激综合征中肠-脑互动紊乱的研究进展

迷走神经是肠-脑轴的重要组成部分,参与调节肠道运动和分泌,人体情绪反应和免疫应答,以及肠易激综合征（IBS）患者的肠-脑互动紊乱。本文就迷走神经及其功能,肠-脑轴中迷走神经功能异常与IBS发病的关系,以及迷走神经在IBS治疗中的应用等方面作一综述,以期提高对迷走神经功能与IBS中肠-脑互动紊乱关系的认识,了解其潜在治疗方法。     

基于脑肠互动理论探究神经营养因子在肠易激综合征中作用的研究进展

肠易激综合征（IBS）是一种常见的功能性胃肠道疾病,无器质性病变,其病理生理机制至今仍未完全清楚。脑肠互动是中枢神经系统与胃肠道之间的双向调节机制,而脑肠互动异常可导致胃肠道感觉、运动和分泌失常,从而引起IBS发病。脑肠互动与神经-内分泌网络密切相关。神经营养因子（NTFs）是一类由神经所支配组织和神经胶质细胞分泌的蛋白质分子,是神经-内分泌网络中的重要组成,主要包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子3(NT-3)和神经营养因子4(NT-4)。其中,NGF、BDNF与IBS的发生关系密切,二者均可通过与相应的特异性受体结合介导脑肠互动异常,从外周介导内脏超敏、参与中枢神经对疼痛增敏以及对精神心理调节等方面参与IBS的病理生理过程,两者作用机制有相似之处,但其介导途径又有所不同;而NT-3、NT-4与IBS的关系目前研究较少,二者作为有可能参与IBS发病的NTFs,其作用途径、作用靶点及作用机制有待于进一步深入研究。     

脑诱发电位与功能性脑成像在肠易激综合征研究中的应用

肠易激综合征(Irritablebowelsyndmme，IBS)是腹部不适或腹痛伴排便异常的一组肠功能障碍综合征，因其缺乏明显形态学及生化异常，病因及发病机制不甚清楚，给诊断及治疗带来了许多困难。近年来，IBS患者内脏感觉异常这一病理生理改变受到广泛关注，为深入了解内脏感觉异常的神经生物学机制，最近几种可客观评价IBS患者感觉传入通路及大脑信息处理过     

从肠易激综合征脑肠轴学说谈肝郁脾虚病理机制

运用肠易激综合征（IBS）脑肠轴学说,探讨中医学对IBS肝郁脾虚病理机制的认识有望是现今该领域的一个突破点.借用功能磁共振成像（fMRI）等技术,已发现IBS患者与疼痛和情感处理有关的脑区域内活动激活状态与健康人明显不同,提示其中枢神经系统对外周疼痛传入的下调功能减弱.     

脑-肠轴失调在肠易激综合征发病中作用的研究进展

肠易激综合征(IBS)的发生是多因素共同作用的结果,其发病机制尚未明确。近年来,以脑-肠轴为基础的生物-心理-社会医学模式参与IBS发病的观念被广泛接受。由神经-内分泌-免疫网络介导的脑-肠双向调节通路,在维持中枢神经系统与肠道局部稳态中发挥重要调节作用,其中任一环节异常,都可能导致稳态平衡破坏而诱发IBS。本文就脑-肠轴失调在IBS发生、发展中作用的研究进展作一综述。     

脑-肠轴在肠易激综合征发病中的作用

肠易激综合征(IBS)的发病可能与肠道动力异常、内脏高敏感、感染、精神心理等有关。脑-肠轴在IBS发病中的作用引起普遍关注,上述的发病因素均可整合到脑-肠互动框架中进行阐述,脑-肠轴成为研究IBS发病机制的切入点。本文从脑-肠轴的概念、作用机制、脑-肠轴功能异常与IBS发病、靶向治疗等方面对脑-肠轴在IBS发病中的作用作一综述。     

肠易激综合征诊治共识意见

肠易激综合征(IBS)是一种以腹痛或腹部不适伴排便习惯改变为特征的功能性肠病，该病缺乏可解释症状的形态学改变和生化异常。IBS的病理生理学基础主要是胃肠动力和内脏感知异常，而造成这些变化的机制尚未完全阐明。已知心理社会因素与IBS发病有密切关系。近年来已注意到肠道急性感染后在易感者中可引起IBS。脑-肠轴神经内分泌调节功能失调以及影响该调节功能的肠道免疫系统的异常，近年来也已受到重视。     

肠易激综合征与心理因素的研究进展

肠易激综合征(IBS)伴发的心理障碍临床多见,且常规治疗的效果不尽如人意。脑肠互动在IBS发病机制中倍受重视。目前强调心理因素的识别和相应的治疗在IBS中的地位。心理治疗中的认知行为疗法和催眠疗法显示了良好的前景,尤其对顽固性IBS患者更为有效。使用三环类抗抑郁剂时应采用极小剂量,并注意个体化。     

肠易激综合征发病机制的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以腹部不适和排便习惯改变为特征的胃肠功能性疾病.IBS的发病机制仍不清楚,传统观点认为基因、心理社会因素、胃肠动力障碍和内脏高敏感性等是引起IBS的关键因素.近年来,人们陆续发现了一些与IBS发病相关的新病理生理学改变依据,如脑肠轴调节失常、肠道感染、肥大细胞的激活并释放活性物质等.本文总结与IBS发病机制相关的一些最新研究进展.     

肠易激综合征脑-肠交互作用模型结肠组织蛋白指纹图谱初探

目的 建立肠易激综合征(IBS)动物模型,利用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)技术分析结肠组织差异蛋白质表达谱,为探索IBS发病机制提供线索.方法 雄性成年Wistar大鼠14只,随机分为模型组和正常组,每组7只.对模型组大鼠采用慢性轻度不可预见性应激联合急性束缚应激制作IBS慢急性联合应激大鼠模型,以行为学方法 评估模型.以MALDI-TOF-MS技术观察大鼠结肠蛋白质伞景,从整体上探索IBS这一功能性肠病有无差异表达蛋白.结果 (1)一般情况:模型组体重低于正常组[(298.88±18.61)g比(348.00±12.44)g,P<0.01];肠道动力:模型组大鼠制模后1 h的排便颗粒数明显多于正常组[(6.00±1.69)粒/1h比(1.14±0.69)粒1 h,P<0.01];行为检测:模型组与正常组相比,糖水消耗量显著减少[(13.63±1.69)ml/1 h比(19.00±3.06)ml/1 h,P<0.05];内脏敏感性:模型组在各个气囊容量下腹肌收缩次数均明显高于正常组(P<0.05).(2)MALDI-TOF-MS 鉴定结果 :模型组与正常组大鼠结肠组织有12个标志蛋白表达有明显差异,分为4类,分别与肠上皮细胞离子分泌、蛋白质合成、G蛋白系统、免疫有关;12种差异表达蛋白在模型组均高于正常组(P<0.05).结论 慢急性联合应激大鼠可部分模拟人类IBS脑-肠交互作用.差异蛋白质的检测为IBS发病机制及治疗靶点的选择提供了参考依据.     

Neuroimaging the brain-gut axis in patients with irritable bowel syndrome

AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.     

Gene, environment, and brain-gut interactions in irritable bowel syndrome

The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain-gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5-hydroxytryptamine (5-HT)-related genes, noradrenaline-related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post-infectious etiology of IBS. Psychosocial stressors and intraluminal factors especially microbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain-gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain-gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin-releasing hormone and 5-HT are the candidate substances which regulate exaggerated brain-gut response. In conclusion, gene x environment interaction together with brain-gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.     

Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis

Background—Recently, several studies have shown analteration in bowel function during sleep in patients with irritablebowel syndrome (IBS), and a recent study also suggests a remarkable increase in rapid eye movement (REM) sleep. These studies have suggested that an alteration in CNS function may play an important rolein the pathogenesis of IBS.
Aims—To confirm the presence of an alteration inREM sleep in patients with IBS and to assess the relation between sleepand a non-invasive measure of gastric functioning, theelectrogastrogram (EGG).
Patients—Ten patients with IBSand 10 age and sexmatched normal volunteers.
Methods—All subjects slept one night in the sleeplaboratory and underwent polysomnographic monitoring to determinesleep patterns, and recording of the EGG from surface electrodes.
Results—The IBS group had a notable andsignificant increase in the percentage and duration of REM sleep(p<0.05). The control group had a decrease in the amplitude of thedominant EGG frequency from waking to non-REM sleep (p<0.05), and asubsequent increase in the amplitude from non-REM to REM sleep(p<0.05). No such changes were noted in the patients with IBS.
Conclusions—Results confirmed the enhancement ofREM sleep in patients with IBS and suggested an intrinsic alteration inautonomic and CNS functioning in patients with IBS.

Keywords:sleep; irritable bowel syndrome; gastric function; brain/gut

     

脑-肠互动指向性条件应激肠易激综合征动物模型的建立

目的建立在肠易激综合征(IBS)发病中符合心理和胃肠生理因素互动特征的动物模型.方法Ⅱ级成年雄性Wistar大鼠作为模型动物,以樟脑丸特殊气味为条件刺激,肢体束缚加结直肠伤害性扩张刺激(气囊内压力＞60 mm Hg)为非条件刺激,建立脑-肠互动指向性条件应激肠功能紊乱模型.以c-Fos表达为标志,研究条件应激过程中的脑活化部位,并观测应激前30 min侧脑室注射促皮质释放因子拮抗剂CRF-9-41对内脏功能的影响.结果条件刺激和非条件刺激结合3次后,条件刺激即可稳定地诱发模型动物肠功能紊乱,持续达2 h以上.与对照组相比,条件刺激后2 h腹壁自发电活动增强[(5.50±0 55)次/5 min比(0.83±0.75)次/5 min,P＜0.01];与对照组[(1.8±0.6)次/5 min]相比,条件应激组近端结肠峰电位增多[(5.7±1.5)次/5min,P＜0.01].条件应激后1 h大脑皮层多个部位c-Fos表达显著升高,其中与对照组[(2.4 ± 1.1/HP)]相比,额前皮质在条件应激组[(30.6±11.5)/HP]和应激组[(35.6±13.5)/HP]表达显著增高(P＜0.05).在条件应激前30 min侧脑室注射CRF-9-41 5μg,显著抑制条件应激诱发的内脏敏感性反应[(5.6±0.9)次/5min比(1.8±0.5)/次5 min,P＜0.01].结论脑-肠互动指向性条件应激可稳定诱发符合IBS发病特征的内脏功能紊乱,该模型可用于脑-肠互动在IBS发病中的作用研究.     

Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls

BACKGROUND: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood. AIM: To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls. METHODS: In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed. RESULTS: ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mumol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group. CONCLUSIONS: We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.     

肠易激综合征的中医虚实证型与血浆脑肠肽水平变化的相关性研究

[目的]观察肝郁气滞型、脾胃虚弱型、肝郁脾虚型肠易激综合征（IBS）患者脑肠肽的变化,探讨IBS的中医虚实证型与血浆脑肠肽水平变化的相关性。[方法]90例IBS患者分为肝气郁滞证组、肝郁脾虚证组、脾胃虚弱证组各30例,正常对照（正常）组10例,应用放射免疫法同批测定血浆血管活性肠肽（VIP）、神经肽Y（NPY）和神经降压素（NT）水平。[结果]3个证型组患者血浆VIP水平显著高于正常组（P〈0.05,〈0.01）;脾胃虚弱、肝郁脾虚证组患者VIP水平显著高于肝气郁滞证组（P〈0.05）,但脾胃虚弱证组和肝郁脾虚证组之间比较差异无统计学意义。3个证型组患者血浆NPY水平显著低于正常组（P〈0.05,〈0.01）,肝郁脾虚证组和肝气郁滞证组NPY水平明显低于脾胃虚弱证组（P〈0.01,〈0.05）,肝郁脾虚证组NPY水平低于肝气郁滞证组,但2组比较差异无统计学意义。3个证型组患者血浆NT水平显著高于正常组（P〈0.01）。3证型间比较差异无统计学意义。[结论]不同中医证型IBS脑肠肽存在不同的变化。IBS的中医病机观与现代医学所倡导的脑-肠轴学说具有相关性。     

The general practitioner''s approach to irritable bowel syndrome: From intention to practice

BACKGROUND: Although general practitioners play a critical role in the management of irritable bowel syndrome because they deal with the most patients, guidelines are developed mainly by specialists. AIMS: To evaluate the clinical features of irritable bowel patients and the general practitioners' approach to irritable bowel syndrome in Italy. SUBJECTS AND METHODS: A questionnaire focusing on the management of this syndrome was completed by 28 general practitioners. Clinical features and diagnostic and treatment measures taken in 229 patients were analysed. RESULTS: Only 35.7% of the general practitioners were familiar with the Rome II criteria. Changes in bowel habits and abdominal pain/discomfort were the most common symptoms. Constipation (74.2%) was more frequent as the main symptom than diarrhoea. Routine blood tests (76.4%) and abdominal ultrasound (42.2%) were requested more frequently than colonoscopy (31.1%). At least one specialist consultation was recommended in 63.3% of patients. Drugs (mainly antispasmodics) were prescribed more frequently for diarrhoea (91.4%) than for constipation (55.7%). CONCLUSIONS: General practitioners are little acquainted with the Rome II criteria. Diagnostic tests and specialist consultations are often recommended; antispasmodics are the most frequently prescribed drug. Guidelines should be developed together by general practitioners and gastroenterologists to effectively manage patients at a lower cost.