Enteroendocrine,Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome

Objectives: The prevalence, gender distribution and clinical presentation of IBS differ between Asian and Western countries. This study aimed at studying and comparing enteroendocrine, Musashi 1 (Msi 1) and neurogenin 3 (neurog 3) cells in Thai and Norwegian IBS patients.

Material and methods: Thirty Thai and 61 Norwegian IBS patients as well as 20 Thai and 24 Norwegian controls were included. Biopsy samples were taken from each of the sigmoid colon and the rectum during a standard colonoscopy. The samples were immunostained for serotonin, peptide YY, oxyntomodulin, pancreatic polypeptide, somatostatin, Msi 1 and neurog 3. The densities of immunoreactive cells were determined with computerized image analysis.

Results: The densities of several enteroendocrine cell types were altered in both the colon and rectum of both Thai and Norwegian IBS patients. Some of these changes were similar in Thai and Norwegian IBS patients, while others differed.

Conclusions: The findings of abnormal densities of the enteroendocrine cells in Thai patients support the notion that enteroendocrine cells are involved in the pathophysiology of IBS. The present observations highlight that IBS differs in Asian and Western countries, and show that the changes in large-intestine enteroendocrine cells in Thai and Norwegian IBS patients might be caused by different mechanisms.     

Eating disorders in patients with irritable bowel syndrome

IntroductionEating disorders (ED) constitute an important group of conditions that commonly occur in adolescents. Gastrointestinal complaints are frequently reported in ED patients. Few studies assessed the association of irritable bowel syndrome (IBS) with ED. The aim of the current study is to determine the prevalence of ED in a group of IBS patients and compare it with a healthy control group and assess the relationship of IBS sub-types, it's duration and severity with ED.Patients and methods100 IBS patients diagnosed according to the Rome-IV criteria and a control group consisting of 100 healthy adults, between 18 and 65 years old, were enrolled in this study. Sub-type, duration and severity of IBS were determined. All participants were requested to fill questionnaires to screen for ED.Results200 subjects participated in the study. 118(59%) were female and 92(41%) were male. The Eating Attitudes Test (EAT) score was significantly higher in the IBS group (Odds ratio: 5.3 CI 95%:4.3–9.3; p < 0.001). The number of subjects with EAT score >30 was significantly higher in the IBS group (p < 0.001). EAT scores were significantly higher in female IBS patients and in younger patients (p = 0.013 and p = 0.043; respectively). No significant association between the IBS sub-type and EAT score was found (p > 0.05). However, IBS severity and duration positively correlated with EAT scores.DiscussionED should be considered in the management of IBS patients. Since many psychological factors can exacerbate IBS symptoms a multidisciplinary approach consisting of medical and behavioral therapeutic modalities should be employed for a better management of these patients.     

Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome

Background and Aim: Although increased mast cells in the gut and their role in visceral hypersensitivity in irritable bowel syndrome have been postulated, this relationship remains unclear. Our aim was to determine whether a relationship exists between the number of mucosal mast cells in the gut and visceral hypersensitivity. Method: Eighteen patients with diarrhea predominant irritable bowel syndrome (D‐IBS) (eight females, 10 males aged 25–65 years; mean 42.6 years) with symptoms meeting the Rome‐II criteria, and 15 healthy controls (five females, 10 males aged 31–57 years; mean 41.4 years) were recruited. Participants completed a questionnaire for bowel symptoms and psychological distress. Colonic mucosal mast cells were identified immunohistochemically and quantified by image analysis, and maximally tolerable pressures were evaluated using barostat test. Results: Numbers of mast cells were significantly greater in the terminal ileum, ascending colon and rectum of D‐IBS patients compared with controls (P < 0.01). A multivariate analysis of the barostat test showed that maximally tolerable pressures of D‐IBS patients were significantly lower than those of controls (P < 0.01). When patients were divided into the rectal hypersensitivity (+) and (–) groups by the distension level of 34 mmHg, mast cell counts were significantly higher in the rectal hypersensitivity (–) group than in the rectal hypersensitivity (+) group for the terminal ileum, ascending colon and rectum (P < 0.05, respectively). Conclusions: Rectal sensitivity was enhanced in D‐IBS patients with moderately increased mucosal mast cells, but it was attenuated in patients with markedly increased ones. This study might provide evidence for an important role of mast cells in visceral hypersensitivity.     

肠易激综合征患者进食前后乙状结肠动力差异的研究

目的研究肠易激综合征(IBS)患者和健康人在空腹和进食状态下不同时段乙状结肠动力的改变.方法符合罗马Ⅱ诊断标准的便秘主导型和腹泻主导型IBS患者各20例及年龄性别匹配的健康志愿者15名(男、女分别为7、8名),分别采用液体灌注测压法记录空腹和进食试餐状态下不同时段乙状结肠移行性高幅突发波、非移行性高幅突发波的波幅及占记录时间百分比的变化;比较乙状结肠在进食前后的动力指数.结果在空腹状态下,腹泻型IBS组乙状结肠动力指数(15.9±4.9)显著高于便秘型IBS组(10.9±5.6)和对照组(9.4±3.6)(P<0.05),主要表现为移行性高幅突发波的波幅和持续时间延长,便秘型IBS组非移行性高幅突发波持续时间也显著延长(P<0.05).进食试餐后30min内,健康组的乙状结肠动力指数(218.7±76.5)升高的幅度更为显著,腹泻组的动力指数(86.5±53.4)改变幅度也显著高于便秘组(42.4±29.6)(P<0.05).试餐后31～60 min,腹泻型IBS组乙状结肠动力指数(65.4±11.7)升高的幅度显著高于便秘组(19.8±14.5)和正常组(23.2±11.3)(P<0.05).结论空腹状态下,腹泻型IBS患者乙状结肠推进性运动增强;胃结肠反射主要表现为蠕动性收缩增强,发生较晚、持续时间较长.便秘型IBS患者胃结肠反射强度弱且消失较快,健康人胃结肠反射出现较早且持续时间较短.     

肥大细胞异型性在肠易激综合征发病机制中的作用研究

目的　探讨肥大细胞在肠易激综合征 (IBS)患者肠道内分布、变化及其临床意义 ,并对其异型性在IBS发病机制中的作用进行相关研究。方法　经结肠镜钳取 2 4名正常人和 5 9例肠易激综合征患者回肠末端、盲肠和降结肠黏膜 ,分别采用抗人肥大细胞类胰酶抗体标识肥大细胞 ,并应用免疫组化方法检测了肥大细胞数目、活性变化和其雌激素受体表达的差异。结果　 1 IBS患者回肠末端和盲肠黏膜肥大细胞数目增多、活性增强 ,降结肠黏膜肥大细胞数目与正常组无显著差别 ,但腹泻型IBS患者降结肠肥大细胞活性增强 (P <0 .0 1)。 2 肥大细胞与雌激素受体阳性 (ER + )细胞显著相关 (R =0 .884,P <0 .0 1) ,但每例肥大细胞和ER +细胞的积分不同。结论　回肠末端和盲肠肥大细胞活性增强提示此处可能为IBS发病的关键部位 ;肥大细胞异型性与IBS病理生理过程密切相关     

Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome

In this multivariate analysis of the irritable bowel syndrome (IBS) we describe the symptomatic and psychologic features of the condition and their possible contributions to health care seeking. We studied 72 IBS patients, 82 persons with IBS who had not sought medical treatment, and 84 normal subjects. All subjects received complete medical evaluation, diary card assessment of abdominal pain and stool habit, and standard psychologic tests of pain, personality, mood, stressful life events, illness behavior, and social support. Pain and diarrhea were the most important symptoms associated with patient status. When controlling for these symptoms we found that (a) IBS patients have a higher proportion of abnormal personality patterns, greater illness behaviors, and lower positive stressful life event scores than IBS nonpatients (p less than 0.001) and normals (p less than 0.001); (b) IBS nonpatients, although psychologically intermediate between patients and normals, are not different from normals (p less than 0.21); and (c) IBS nonpatients have higher coping capabilities, experience illness as less disruptive to life, and tend to exhibit less psychologic denial than patients. These factors may contribute to "wellness behaviors" among people with chronic bowel symptoms. We conclude that the psychologic factors previously attributed to the IBS are associated with patient status rather than to the disorder per se. These factors may interact with physiologic disturbances in the bowel to determine how the illness is experienced and acted upon.     

Immune activation in patients with irritable bowel syndrome

BACKGROUND AND AIMS: We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines. METHODS: We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale. RESULTS: IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS. CONCLUSIONS: Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.     

True Chromogranin A concentrations in plasma from patients with small intestinal neuroendocrine tumours

Abstract

Objective: The incidence of enteropancreatic neuroendocrine tumours (NET) is increasing. Chromogranin A (CgA) in plasma is a marker in patients suspected of NET tumours. CgA, however, is a precursor protein subjected to cellular processing that challenges quantitation and hence the use of CgA in diagnostics.

Materials and methods: CgA concentrations in plasma sampled from 130 well-characterized patients with small intestinal NETs and from 30 healthy subjects were measured with eight commercial CgA kits, an in-house radioimmunoassay (RIA) and a processing-independent assay (PIA). For the evaluation of diagnostic accuracy, we performed regression analyses and plotted receiver-operating characteristic curves (ROC). The specificity was further assessed by size chromatography.

Results: Five commercial assays (Thermo-Fisher, DRG Diagnostics, Eurodiagnostica (RIA and ELISA), and Phoenix), displayed a diagnostic accuracy with area under the curve (AUC) values >0.90, whereas three immunoassays (Yanaihara, CisBio RIA, and CisBio ELISA) discriminated poorly between disease stages (AUC: 0.60–0.78). Compared with the in-house assays, however, even the most accurate commercial immunoassay still missed patients with metastatic disease. Chromatography showed non-uniform patterns of large and small CgA fragments in plasma.

Conclusion: Available commercial immunoassays measure CgA in plasma with gross variability. Three commercial CgA immunoassays discriminate so poorly between health and disease that they should not be used. The highest diagnostic accuracy was obtained with processing-independent measurement of total CgA concentrations in plasma.     

Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study

Abstract

Objective. To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. Material and methods. A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn’s disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. Results. Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in ‘biologic’ group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the ‘conventional’ treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. Conclusion. CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.     

Dysmotility of the small intestine in irritable bowel syndrome.

Though the pathophysiology of the irritable bowel syndrome (IBS) is commonly attributed to dysfunction of the large intestine, evidence exists to incriminate the small bowel. In order to further explore the role of the small bowel in IBS several stimuli were applied, in an attempt to unmask the dysmotility of the jejunum and ileum. These included infusions of cholecystokinin-octapeptide (CCK-OP), a high fat meal, neostigmine and balloon distension of the ileum. Three groups (n = 8) each of age and sex matched healthy volunteers were studied; patients with IBS complained of predominant constipation (n = 8) or diarrhoea (n = 8). Patients with IBS responded excessively to stimulation by CCK-OP, fatty meal, and ileal distension. In general patients with diarrhoea were more sensitive to stimuli than those with constipation. The ileum responded more to stimulation than the jejunum. As in the large bowel, stimuli appear to unmask intestinal dysmotility in patients with IBS. Motor abnormalities were often accompanied by abdominal symptoms, raising the possibility that dysfunction of the small bowel contributes to the symptoms of IBS.     

肠易激综合征乙状结肠移行性运动与胃肠肽胆囊收缩素、胃动素的相关性研究

目的研究肠易激综合征(IBS)患者乙状结肠移行性运动与胃肠肽胆囊收缩素(CCK)、胃动素(MTL)的关系,探讨CCK、MTL对IBS患者乙状结肠动力的调节作用。方法对2004年3月至2005年2月,在广西壮族自治区人民医院消化内科住院,符合罗马Ⅱ诊断标准的腹泻型(D-IBS)和便秘型(C-IBS)IBS患者各20例及年龄、性别匹配的健康志愿者组15名(男7名、女8名),分别采用毛细管液体灌注测压法记录空腹状态下乙状结肠移行性高幅突发波的波幅及占记录时间百分比;同时采用放射免疫法测定所有研究对象血浆和乙状结肠黏膜CCK、MTL的含量。结果D-IBS组乙状结肠移行性高幅突发波的波幅和持续时间显著高于C-IBS组和健康组(P<0.05),D-IBS组血浆MTL、CCK浓度显著高于C-IBS组和健康组(P<0.01),黏膜MTL显著高于C-IBS组和健康组(P<0.01)。IBS患者乙状结肠移行高幅突发波的波幅和持续时间与血浆或黏膜CCK、MTL分别呈正相关(P<0.05)。结论IBS患者乙状结肠移行性运动可能受血浆CCK、黏膜和血浆MTL浓度相关的正性调节作用。     

Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome

Irritable bowel syndrome(IBS)is a common functional gastrointestinal(GI)disorder characterized by unspecific symptoms.In clinical practice it is crucial to distinguish between non-inflammatory functional problems and inflammatory,malignant or infectious diseases of the GI tract.Differentiation between these involves the use of clinical,radiological,endoscopic,histological and serological techniques,which are invasive,expensive,time-consuming and/or hindered by inaccuracies arising from subjective components.A range of faecal markers now appears to have the potential to greatly assist in the differentiation of inflammatory bowel disease(IBD)and IBS.Faecal markers of neutrophil influx into the mucosa are reliable indicators of intestinal inflammation and their role has been mainly studied in discriminating IBD from non-IBD conditions(including IBS)rather than organic from non-organic diseases.Phagocytespecific proteins of the S100 family(S100A12,calprotectin)are amongst the most promising faecal biomarkers of inflammation.Faecal leukocyte degranulation markers(lactoferrin,polymorphonuclear elastase and myeloperoxidase)have also been suggested as diagnostic tools for the differentiation of IBD and IBS.More recently,additional proteins,including granins,defensins and matrix-metalloproteases,have been discussed as differential diagnostic markers in IBD and IBS.In this review,some of the most promising faecal markers,which have the potential to differentiate IBD and IBS and to advance diagnostic practices,will be discussed.     

Pathogenesis of irritable bowel syndrome: The mast cell connection

The effect of experimental amyloidosis on the morphology of the Paneth cells of the mouse was investigated by using light and fluorescence microscopy. Amyloidosis was induced by daily subcutaneous casein injections for 4 weeks. It was found that the number of secretory granules of the Paneth cells increased in the jejunum, but remained normal in the duodenum. Small morphological alterations took place in the Paneth cells during the induction of amyloidosis, and occasionally the Paneth cells were totally lost. These changes suggest that the function of the Paneth cells of the jejunum may be partly inhibited during experimental amyloidosis.     

Bowel urgency in patients with irritable bowel syndrome

BACKGROUND & AIMS: Bowel urgency is the most bothersome symptom in irritable bowel syndrome patients with diarrhea, but its pathophysiology is poorly understood. Our aim was to assess the relationships among reporting the symptom, the reservoir functions of the colon and rectum, and the patients' psychologic profile. METHODS: The study involved 28 consecutive patients with irritable bowel syndrome and 17 healthy subjects. The presence or absence of bowel urgency was verified by means of a questionnaire during the 3 days required for the ingestion of radio-opaque markers. On the fourth day, an abdominal x-ray was taken to assess colonic transit time, and rectal sensory and motor responses were measured during rectal distention. The subjects' psychologic profiles were assessed using a psychologic symptoms checklist. RESULTS: Forty-six percent of the patients reported urgency associated with at least 1 defecation. The multivariate logistic regression analysis showed that colonic transit was the only variable independently associated with reported bowel urgency, but the threshold for the sensation of urgency was not removed from the model since its borderline significance level. Rectal compliance was closely associated with the threshold for the sensation of urgency during rectal distention but was not an independent factor for reporting the sensation. The patients with and without urgency showed altered psychologic profiles. CONCLUSIONS: The symptom of urgency is associated with objective alterations in the colonic and rectal reservoir of patients with irritable bowel syndrome.     

Recent developments in the pathophysiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.     

Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome

Previous findings suggested an involvement of mast cells in the pathogenesis of irritable bowel syndrome (IBS). The pathophysiological significance of mast cells is defined both by their number in tissue and by their activity. In the present pilot study activity of mast cells in patients with therapy-resistant IBS was investigated for the first time systematically. Twenty patients with therapy-resistant IBS were investigated for the presence of a pathologically increased mast cell mediator release by means of a validated structured interview suitable to identify mast cell mediator-related symptoms and by determing selected surrogate parameters for mast cell activity. Nineteen of the 20 patients presented mast cell mediator-related symptoms. Pathologically increased mast cell activity-related coagulation and fibrinolysis parameters were detected in 11 of 12 patients investigated in that regard. One patient had an elevated level of methylhistamine in urine. The present data provide evidence that in patients with therapy-resistant IBS a pathologically increased systemic mast cell activity may occur with high prevalence. This finding fits to the idea of an assumed contribution of activated mast cells in the pathophysiology of IBS.     

肠易激综合征病人肠道气体定量分析

目的　通过X线腹部平片对肠道气体进行定量测试 ,分析肠道气体容量与肠易激综合征(IBS)的关系。方法　 4 8例根据罗马Ⅱ标准诊断的IBS病人和 2 5例正常对照的X线腹部平片经数字化转换后输入电脑 ,肠道气体量在电脑显示为象素值 ,经体格标准化后 ,以气体容量积分 (GVS)表达。以对照GVS的 x± 2s为正常值 ,分析GVS与IBS型别的关系。结果　正常对照GVS为 0 .0 5 5±0 .0 12 ,离散系数为 2 1.8% ;便秘型IBS均值 (0 .0 76± 0 .0 2 7,t =3.5 99,P <0 .0 1)与正常人比较显著增高 ,4 4 .4 %的个体GVS大于正常值 ,余在正常范围 ;腹泻型IBS均值 (0 .0 4 8± 0 .0 32 ,t =1.4 76 ,P >0 .0 5 )与正常人比较差异无显著性 ,但离散系数高达 6 6 .7% ,4 2 .9%的病人GVS降低 ,14 .3%增高。结论　IBS病人肠道气体容量存在明显改变 ,并与型别有关 ;便秘型以增多为主 ,腹泻型以减少为主。     

Do patients with irritable bowel syndrome in primary care really differ from outpatients with irritable bowel syndrome?

Background—Little is known about the comparabilityof outpatients with irritable bowel syndrome (IBS) and patients withIBS in primary care with regard to severity of complaints,perceived limitations, other aspects of the complaints, and sex differences.
Aims—To compare outpatients with IBS with primarycare patients with IBS.
Patients—One hundred and nine patients with IBSwere recruited from general practices in Amsterdam and 86 patients withIBS were recruited from the outpatient clinic of the Department of Internal Medicine of the University Hospital in Nijmegen.
Methods—Each patient completed a questionnaire ondemographic variables, abdominal complaints, related complaints, andattributed causes of their abdominal complaints. The scores of the twogroups were compared by univariate and multivariate analysis.
Results—The outpatient group containedsignificantly more men, reported more severe abdominal pain, morefrequent complaints, more interference with daily activities, and ahigher degree of avoidance of activities (p<0.01) than the primarycare group. When each sex was analysed separately, these differencesremained for female (p<0.01) but not for male patients. Outpatientswere more likely to attribute their complaints to somatic causes(p<0.01), whereas primary care patients were more likely to attributetheir complaints to stress (p<0.01) or their agitated way of life(p<0.05). Multivariate analysis showed that a high severity score, alarge number of additional complaints, and a low score on the stress attribution were important determinants for being in the outpatient group.
Conclusions—Female outpatients consider theircomplaints to be more serious and interfering than do patients with IBSin primary care. Male outpatients were comparable to primary carepatients with IBS. More research needs to be done into sex specificdifferences in IBS and into the factors that influence the decision torefer a patient with IBS.

     

肠易激综合征患者内脏高敏感性的机制研究

目的检测肠易激综合征(IBS)患者的内脏感觉及其结肠黏膜肥大细胞(MC)、P物质(SP)和血管活性肠肽(VIP)的改变,探讨MC、SP、VIP对IBS患者内脏高敏感性的作用及其机制.方法黏膜标本取自19例正常人和22例腹泻型IBS(D-IBS)、20例便秘型IBS(C-IBS)患者回肠末端、回盲部、升结肠、乙状结肠,应用特殊组织化学染色法、免疫组织化学染色法分别对MC、SP和VIP免疫反应阳性神经纤维进行染色,应用彩色病理图像分析软件进行分析,电镜观察MC及其毗邻结构;应用电子气压泵及灌注导管测压仪检测上述患者肛门直肠压力、直肠对容量刺激的感觉及直肠顺应性.结果IBS组回肠末端、回盲部、升结肠MC明显增多,MC显著变异(P＜0.01);IBS组结肠黏膜SP、VIP免疫反应阳性神经纤维较正常对照组增多、增粗、阳性强度增强(P＜0.01);IBS组SP、VIP免疫反应阳性纤维的阳性强度均值、面积与MC的密度、面积密切相关(r=0.3860～0.6632,P＜0.01、P＜0.05),并可观察到MC与无髓神经末梢及浆细胞等内分泌细胞毗邻或密切接触;IBS组肛门直肠括约肌的静息压、收缩压、松弛压与正常对照组相似(P＞0.05),感觉阈值、排便阈值、疼痛阈值明显低于正常对照组(P＜0.01),直肠顺应性降低(P＜0.01),向直肠内注气20或40 ml后均可引起直肠肛门抑制性反射.结论MC、SP、VIP在IBS的病理生理机制中可能起关键性作用,MC活性、SP、VIP免疫反应阳性神经纤维可能与IBS以内脏感觉及动力变化为特征的内脏高敏感性相关联.