腹泻型肠易激综合征患者肠黏膜一氧化氮含量变化初步探讨

目的:探讨NO在肠易激综合征(IBS)发病机制中的作用。方法:①应用电子气压泵及灌注导管测压仪研究25例腹泻型IBS患者及15例正常人的肛门、直肠压力、直肠顺应性、乙状结肠和直肠运动指数以及直肠对容量刺激的感觉阈值;②应用硝酸还原酶法测定两组肠黏膜NO的含量。结果:     

肠易激综合征患者肛门直肠感觉阈值和动力学的改变

采用PC Polygraf HR高分辨多道胃肠功能测定仪,检测42例肠易激综合征(IBS)患者的肛门直肠压力、直肠容量感知、疼痛阈值、耐受阈值等指标,并与15例健康人做对照.结果发现IBS的直肠静息压、肛管括约肌静息压、最大缩窄压及肛管长度与对照组无显著性差异(P＞0.05),而初始感觉阈值、疼痛阈值、排便阈值腹泻组低于正常对照组(P＜0.05),便秘组高于正常对照组(P＜0.05).排便时IBS便秘组患者的肛管松弛压高于正常对照组(P＜0.05).提示IBS患者排便功能和直肠感觉功能存在异常.     

便秘型肠易激综合征患者结、直肠肛门动力学的临床研究

目的研究便秘型肠易激综合征患者结肠、直肠动力,直肠感觉功能.方法用结肠传输试验检测结肠传输时间,并用结肠传输指数分型,用肛门直肠测压方法测定便秘型IBS直肠静息压,肛管静息压,肛门括约肌最大缩榨压,模拟排便时,直肠收缩压,肛门括约肌剩余压,直肠对容量扩张刺激的初始感觉阈值,最大耐受容量,直肠顺应性.结果便秘型IBS患者全结肠及各节段结肠传输时间均高于对照组,便秘型IBS患者肛管静息压,直肠静息压与对照组无差异(P＞0.05),肛门括约肌最大缩榨压低于正常对照组,最大耐受容量及直肠顺应性均明显高于对照组(P＜0.01),且发现不同传输类型的便秘型IBS肛门直肠测压表现不同.结论便秘型IBS患者存在结肠、肛门直肠动力及直肠感觉功能异常,结肠传输试验与肛门直肠测压相结合,可体现不同传输类型便秘型IBS肛门直肠动力学病因机制.     

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.     

老年肠易激综合征患者肠黏膜肥大细胞与血管活性肠肽的表达及意义

目的探讨肠易激综合征(IBS)患者肠黏膜肥大细胞(MC)及血管活性肠肽(VIP)的表达及其可能作用。方法 33例腹泻型IBS患者(D-IBS组)、27例便秘型IBS患者(C-IBS组)及18例健康体检者(对照组)纳入研究。分别取回盲部、乙状结肠黏膜行VIP免疫组织化学染色和甲苯胺蓝染色MC计数,检测肛管直肠压力。结果 1D-IBS组和C-IBS组乙状结肠部MC计数均较回盲部显著降低(P<0.05),两组间各部MC计数比较无统计学差异(P>0.05),但各部位均较对照组显著增高(P<0.05)。2D-IBS组和C-IBS组回盲部和乙状结肠黏膜VIP表达无统计学差异(P>0.05),但各部位均较对照组显著增高(P<0.05)。3三组间静息压、最大收缩压及松弛压均无统计学差异(P>0.05)。D-IBS组和C-IBS组患者感觉阈值、最大容量阈值及疼痛阈值均无统计学差异(P>0.05),但与对照组比较均显著降低(P<0.05)。结论 IBS患者结肠黏膜MC和VIP表达增加,可能对IBS患者内脏高敏感性的形成有一定影响。     

肠易激综合征便秘型和功能性便秘结、直肠肛门动力学研究

目的 研究肠易激综合征(IBS)便秘型和功能性便秘患者结肠、直肠动力,直肠感觉功能.方法 对IBS便秘型患者52例和功能性便秘患者48例进行肛门直肠测压检查,并做结肠传输试验.同时选择正常健康人作对照组.结果 IBS便秘型组和功能性便秘组与对照组间直肠静息压、肛管静息压和肛门括约肌最大缩榨压比较均未见明显差异.IBS便秘型组初感阈值及排便阈值(75.00±34.04 ml,117.31±37.60 ml)较正常对照(97.14±20.54 ml,138.57±19.94 ml)明显降低.功能性便秘组排便阈值及最大耐受阈值(187.92 ±68.62 ml,252.5±93.40ml)较正常对照组(138.57±19.94 ml,181.43±18.34 ml)明显升高.IBS便秘型组各项感觉阈值较功能性便秘组均明显降低.功能性便秘组较IBS便秘型组患者结肠传输试验符合出口梗阻的比例高,但无统计学差异.结论 IBS便秘型直肠感觉过敏,功能性便秘直肠感觉迟钝.     

腹泻型与便秘型肠易激综合征直肠肛管动力和感觉功能的不同特点

目的 研究腹泻型与便秘型肠易激综合征（IBS）病人直肠肛管动力和直肠感觉功能的不同特点。方法 选择IBS病人85例，分成两组。其中腹泻组52例，便秘组33例，20例健康志愿者为对照组，采用PC Polygraf ID高分辨率多道胃肠功能测定仪，分别测定直肠肛管压力、直肠感知阈值、排便阈值、最大耐受量和直肠肛门抑制反射最低充气量。结果IBS病人的直肠静息压、肛管静息压和直肠肛门抑制反射最低充气量与健康对照组比较无显著性差异。腹泻组的最大缩窄压和排便阈值显著低于健康对照组。便秘组的松弛压、直肠感知阈值、排便阈值和最大耐受量显著高于健康对照组。结论腹泻型IBS病人的症状与最大缩窄压和排便闽值降低有关；而便秘型则与松弛压、直肠感知阈值、排便阈值和最大耐受量显著增高有关。     

慢性特发性便秘患者肛门直肠的动力改变

目的　测定慢性特发性便秘患者肛门直肠压力 ,探讨肛门直肠动力障碍在便秘发病机制中的作用。方法　采用美国Sandhill公司生产的BioLAB动力学参数监测系统及固态压力传感器导管 ,对 40例CIC患者进行肛门直肠压力测定 ,并与 40例正常人进行对比。结果　便秘组肛管静息压、最大缩榨压、最大缩榨间期及缩榨指数均明显低于对照组 (P <0 0 5 ,P <0 0 5 ,P <0 0l,P<0 0 1) ;模拟排便动作时肛管剩余压明显高于对照组 (P <0 0 0 1) ,肛管松弛率、排便指数均低于对照组 ,统计学处理具有显著性差异 ;初始感阈值容量大于对照组 (P <0 0 0 1) ,排便感阈值大于对照组 (P <0 0 5 ) ,最大耐受量明显低于对照组 (P <0 0 1)。结论　慢性特发性便秘病人存在肛管直肠的动力学异常及直肠敏感性降低     

老年糖尿病便秘患者肛门直肠动力学特点及影响因素

目的探讨合并糖尿病的老年便秘患者肛门直肠动力学的变化及其影响因素。方法老年糖尿病便秘患者65例为观察组,男35例,女30例,平均年龄(75. 6±7. 2)岁;对照组为无糖尿病的老年便秘患者97例,男73例,女24例,平均年龄(76. 2±8. 6)岁。采用灌注式肛门直肠测压装置测定患者肛管静息压、肛管最大缩榨压、初始感觉阈值、首次便意感阈值、最大耐受容量。结果观察组肛管静息压明显低于对照组(t=2. 112,P=0. 036);其初始感觉阈值、首次便意感阈值及最大耐受容量均明显高于对照组(P0. 05)。合并糖尿病的男性老年便秘患者肛管最大缩榨压明显高于女性(t=3. 801,P=0. 000)。伴腹痛的老年糖尿病便秘患者的肛管静息压显著高于不伴腹痛者(t=3. 289,P=0. 002);伴排便不尽感的老年糖尿病便秘患者肛管最大缩榨压、首次便意感阈值及最大耐受容量均明显高于无排便不尽感患者(P0. 05)。结论糖尿病老年便秘患者肛门直肠动力学变化有其特点,性别及腹痛、排便不尽感是肛门直肠动力学变化的影响因素。     

肠易激综合征患者肠黏膜肥大细胞与神经纤维的关联

目的　探讨肠黏膜肥大细胞与神经纤维之间的关联及其与肠易激综合征 (IBS)发病的关系。方法　应用电镜和免疫组化双重染色技术 ,对 5 6例符合罗马Ⅱ标准的腹泻型IBS患者和 12例非IBS对照组患者末端回肠和直肠 乙状结肠交界部位肠黏膜内的肥大细胞与神经纤维的关联进行了检测。结果　IBS患者和对照组肠黏膜内多数肥大细胞与神经纤维紧邻。患者末端回肠、直肠 乙状结肠交界处黏膜内神经元特异性烯醇化酶 (NSE)、P物质、5 羟色胺 (5 HT)的表达明显高于对照组 (P <0 .0 5 ) ,肥大细胞周围NSE、P物质、降钙素基因相关肽 (CGRP)、5 HT的表达也明显增强。IBS患者末端回肠黏膜内肥大细胞的数目 (10 .98± 2 .96 )与对照组 (6 .0 5± 0 .5 1)相比明显增多 (P <0 .0 1)。IBS患者与对照组相比 ,末端回肠内NSE(6 .73± 1.0 2比 4 .2 5± 0 .5 0 )、P物质 (6 .84± 0 .85比 4 .2 8± 0 .4 0 )、CGRP(6 .73± 0 .82比 4 .33± 0 .5 4 )、5 HT(6 .72± 0 .81比 4 .0 0± 0 .6 3)阳性神经纤维紧邻的肥大细胞数目亦明显增多 (P <0 .0 1)。结论　IBS患者肠黏膜内肥大细胞数量的增多及其周围神经肽表达的增强表明 :免疫系统与肠神经丛之间通路的活化可能与IBS的发病有关。     

腹部冷刺激对肠易激综合征患者内脏感觉阈值的影响

目的 探讨腹部冷刺激对肠易激综合征（IBS）患者内脏褡珠影响。方法 通过脐部放置冰袋加直肠球囊内充气（时相性）和直肠球囊内注入冰水，观察46例IBS患者症状变化及直肠初始感觉阈值和排便阈值，并与13例健康人对照。结果 （1）脐部放置冰袋加直肠球囊内充气可诱发部分患者症状的产生，如腹痛、腹部不适等，但对初始感觉阈值和排便阈值无明显影响。（2）直肠球囊内注入冰水后，除便秘型IBS的排便阈值稍有所增加但差异不显著外，其余患者初始感觉阈值及排便阈值均明显低于对照组，以腹泻型变化最明显。结论 腹部冷刺激对IBS患者内脏感觉阈值无明显影响，而直肠内冷刺激可明显降低初始感觉阈值，说明IBS患者感觉过敏并非整体痛阈降低所致，而仅指内脏感觉过敏。     

Study on functional constipation and constipation‐predominant irritable bowel syndrome by using the colonic transit test and anorectal manometry

OBJECTIVE: To investigate the visceral perception, anorectal pressure and colonic transit time (CTT) in patients with functional constipation and constipation‐predominant irritable bowel syndrome (C‐IBS), and to study the manometric abnormalities of these two conditions. METHODS: The CTT in patients with functional constipation and C‐IBS was studied by using radiopaque markers. Rectal visceral perception thresholds, rectal compliance and anorectal pressure were examined by electric barostat. RESULTS: The CTT in both groups of constipated patients was abnormal. A lot of radiopaque markers remained in the right colon in C‐IBS patients, whereas in patients with functional constipation, the radiopaque markers remained in each segment of the colon. The anorectal resting pressure, squeezing pressure and relaxation pressure were normal in both groups. Rectal compliance and defecation thresholds were much higher compared with controls, and the rectal visceral perception of functional constipation was also abnormal. CONCLUSIONS: The motility abnormalities of functional constipation and C‐IBS occurred in different colonic segments. Results suggest that CTT measure­ment and anorectal manometry could be helpful in the differential diagnosis of these two conditions.     

The pathophysiology of irritable bowel syndrome: inflammation and motor disorder]

Irritable bowel syndrome (IBS) is one of the most common disorders and a heterogeneous condition in view of symptoms and underlying mechanisms. Though underlying causes of pathophysiologic changes remain unclear, low grade mucosal inflammation and abnormal intestinal motility are accepted mechanisms which alter gut function and generate symptoms of IBS. First, before 1980s, abnormal colonic and rectal motor functions were regarded as the main pathophysiology of IBS, but only 25-75% of IBS patients have apparent motor abnormalities which differ from the motor functions in normal controls. So, various gastrointestinal motility tests were not indicated for the diagnosis of IBS. The high-amplitude propagating contractions of colon in IBS patients may be related to the visceral pain perception. Second, the low grade mucosal inflammation may be involved in the pathophysiology of visceral hypersensitivity. Post infectious IBS (PI-IBS) occupied 6-17% of the total IBS and some previous prospective studies reported that 7-33% of acute bacterial enteritis patients developed IBS after 6-12 months of infection. The relative risk of IBS in the gastroenteritis cohort was 11.9 and the strongest risk factor is the duration of diarrhea. After enteritis event, the increased number of immunocytes, mast cells and large amount of lymphocytes infiltration were revealed in mucosa and enteric nervous system of the gut. Beside the inflammatory cells, enterochromaffin cells, cytokines and inducible nitric oxide may be related to the pathophysiologic mechanism of PI-IBS. Lastly, the abnormalities in the gastrointestinal autonomic nervous system can induce constipation or motor disorders, but further research should elucidate it.     

Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome

Background Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). This study sought to investigate rectal sensitivity and abdominal symptoms in IBS patients before and after 220 ml cold water intake. Methods A total of 60 IBS patients and 18 healthy controls participated in this study. Both the perception thresholds and defecation thresholds to rectal balloon distension were measured. Then, all subjects were asked to drink 220 ml 37°C warm water or 4°C cold water, and these steps were repeated 20 min later. Symptoms including abdominal pain/discomfort, bloating, and diarrhea were recorded during the study. Results Compared with the controls, the thresholds of initial sensation to rectal balloon distention in IBS patients were significantly lower while the defecation thresholds were higher in constipation-predominant IBS patients. After drinking cold water, the perception thresholds in IBS patients and the defecation thresholds in diarrhea-predominant IBS patients were further decreased. However, warm water intake did not change the perception thresholds significantly in either IBS patients or controls. A negative linear correlation was found between the symptoms and the visceral perception thresholds in diarrhea-predominant IBS patients who showed significant symptoms after cold water intake. Conclusion The results indicated that cold water intake leads to lowered visceral perception thresholds in IBS patients that were inversely relevant to the abdominal symptoms in symptomatic diarrhea-predominant IBS patients. The alteration of rectal sensitivity and abdominal symptoms following cold water stimulation provided further objective evidence for visceral hypersensitivity in IBS patients.     

直肠内温度变化影响肠易激综合征患者内脏感觉阈值

目的 探讨直肠内温度及压力变化对肠易激综合征(IBS)患者内脏感觉阈值的影响，进一步研究IBS的发病机制。方法 通过直肠球囊内注入空气(压力刺激)、38℃温水、4℃冰水(温度刺激)及脐部放置冰袋加直肠球囊内充气，研究直肠温度和压力变化刺激对初始感觉阈值和排便阈值的影响。结果 (1)直肠球囊内注气后，IBS组患者的初始感觉阈值明显低于对照组，排便阈值差异不明显。IBS组中腹泻型与交替型患者的初始感觉阈值及排便阈值均明显降低；便秘型患者的初始感觉阈值稍低于对照组，排便阈值明显增高。(2)直肠球囊内注入4℃冰水后，除便秘型IBS的排便阈值稍有所增加外，其余患者初始感觉阈值及排便阈值均显著降低，以腹泻型变化最明显。(3)脐部放置冰袋可诱发部分患者产生症状，但对初始感觉阈值和排便阈值无明显影响。结论 直肠温度和压力刺激可明显降低IBS患者的初始感觉阈值和排便阈值，以腹泻型患者最显著。内脏对压力和温度的敏感性增高可能是IBS发病的重要机制之一。     

SSTR1和SSTR2在肠易激综合征和活动期溃疡性结肠炎患者结肠黏膜中的表达及其临床意义

生长抑素是胃肠道重要神经递质之一,其功能的发挥是由生长抑素受体（SSTR）介导的,SSTR表达水平与多种胃肠道疾病有关。目的：研究SSTR1、SSTR2在肠易激综合征（IBS）和活动期溃疡性结肠炎（UC）患者结肠黏膜中的表达及其临床意义。方法：收集腹泻型IBS（IBS—D）、便秘型IBS（IBS—C）、活动期UC患者和正常对照者各30例,记录患者的症状发生时间、严重程度并评分。以免疫组化方法检测活检结肠黏膜中SSTR1、SSTR2的表达。结果：SSTR1、SSTR2的表达位于上皮组织的上皮细胞和间质淋巴细胞的细胞膜和细胞核中。正常结肠黏膜组织中两者均为弱阳性表达,IBS组和UC组SSTR2表达阳性率和免疫组化评分显著高于正常对照组（P〈0．05）。各组中SSTR1、SSTR2免疫组化评分均呈线性正相关（P〈0．05）。SSTR1、SSTR2的表达与IBS—D的腹泻病程和程度以及UC的便血程度相关（P〈0．05）,SSTR2的表达与IBS-C的便秘病程和程度相关（P〈0．05）。结论：SSTR1、SSTR2在正常结肠黏膜中为弱阳性表达．两者在IBS和UC的发病中起有一定作用。UC与IBS—D在发病机制上可能存在一定关联。     

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

BACKGROUND AND AIMS: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. METHODS: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). RESULTS: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. CONCLUSION: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.     

Visceral hypersensitivity in irritable bowel syndrome

Altered central processing, abnormal gastrointestinal motility and visceral hypersensitivity may be possible major pathophysiology of irritable bowel syndrome (IBS). These factors affect each other and are probably associated with development of IBS symptoms. It has been confirmed that lower pain threshold to colonic distention was observed in most of patients with IBS than healthy subjects. We have investigated pain perception of the descending colon among different subtypes of IBS. There was no difference in pain threshold to colonic distention between IBS with diarrhea and constipation. Some brain regions such as the anterior cingulate cortex (ACC) may play a major role for generating pain and/or pain-related emotion in humans. IBS patients showed greater activation in the perigenual ACC during painful rectal distention compared with healthy subjects. Inflammation, stress and the combination of both stimuli can induce significant increase in visceral sensitivity in animal models. Serotonin (5-HT) can modulate visceral perception. It has been thought that 5-HT(3) receptors may play an important role for conveying visceral sensation from the gut. Corticotropin-releasing hormone (CRH) may also modulate visceral pain hypersensitivity in IBS. CRH receptor-1 antagonist significantly prevented an increase in gut sensitivity in rats. It has been demonstrated that non-specific CRH receptor antagonist α-helical CRH significantly reduced abdominal pain score during gut stimulus in patients with IBS. In conclusion, visceral hypersensitivity is common in IBS patients and probably plays a major role in development of the symptoms and both central and peripheral factors may enhance the pain sensitivity.     

Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome

BACKGROUND & AIMS: The pathophysiology of irritable bowel syndrome (IBS) remains enigmatic; abnormalities in serotonin metabolism have been implicated. Two proteins that influence the function of serotonin and serotonergic receptors are serotonin transporter protein (SERT or soluble carrier protein, SLC6A4) and p11 (S-100A10, or calpactin I light chain). Both proteins are reported to be associated with depression-like states, a frequent comorbid condition in IBS. We explored the hypothesis that expression of these 2 proteins in colonic and rectal mucosa is abnormal in patients with IBS as compared with healthy controls. METHODS: Messenger RNA (mRNA) expression of SLC6A4 and p11 was measured in sigmoid and rectal mucosal biopsy specimens. Genotype of the promoter for SLC6A4 was also assessed in all participants. Validation studies explored reproducibility of 2 biopsy specimens taken from the same region and biopsy specimens taken an average of approximately 3 months apart. RESULTS: We found normal colonic mucosal expression of SLC6A4 in diarrhea (IBS-D)- or constipation-predominant IBS (IBS-C). On the other hand, p11 expression was increased in IBS. No significant effect on p11 mRNA expression in sigmoid colon or rectum was noted from antidepressant treatment in any of the analyzed subgroups. CONCLUSIONS: Colonic mucosal expression of SLC6A4 in IBS is normal. Given that overexpression of p11 can increase serotonergic receptor functions (eg, 5-HT(1B) receptors), these data support the need for further study of the interaction between p11 expression in health and disease and its role in the therapeutic response to serotonergic agents, including antidepressants.