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。     

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.     

Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?

BACKGROUND & AIMS: Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses. METHODS: The scientific literature since 1966 in all languages cited in Medline was systematically reviewed. RESULTS: Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%). CONCLUSIONS: Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.     

Probiotics in functional bowel disorders

Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.     

匹维溴铵对肠易激综合征患者回盲部肥大细胞的脱粒影响

目的评价选择性肠道钙离子拮抗剂匹维溴胺对肠易激综合征（Irritable Bowel syndrome,IBS）的临床疗效以及对回盲部肥大细胞脱粒的影响,探讨其治疗IBS的可能机制。方法应用匹维溴胺治疗符合入选标准的IBS患者48例,观察其疗效并检测治疗前后IBS患者回盲部脱颗粒肥大细胞的数目变化。结果匹维溴胺治疗腹泻型IBS疗效明显,治疗前后腹泻型IBS患者脱颗粒肥大细胞数目有显著变化。结论匹维溴胺治疗腹泻型IBS有效,可能抑制了肥大细胞的脱粒活化,机理有待于进一步探讨。     

Alterations in the brain-gut axis underlying visceral chemosensitivity in Nippostrongylus brasiliensis-infected mice

BACKGROUND & AIMS: Visceral hypersensitivity, a hallmark of irritable bowel syndrome, is generally considered to be mechanosensitive in nature and mediated via spinal afferents. Both stress and inflammation are implicated in visceral hypersensitivity, but the underlying molecular mechanisms of visceral hypersensitivity are unknown. METHODS: Mice were infected with Nippostrongylus brasiliensis (Nb) larvae, exposed to environmental stress and the following separate studies performed 3-4 weeks later. Mesenteric afferent nerve activity was recorded in response to either ramp balloon distention (60 mm Hg), or to an intraluminal perfusion of hydrochloric acid (50 mmol/L), or to octreotide administration (2 micromol/L). Intraperitoneal injection of cholera toxin B-488 identified neurons projecting to the abdominal viscera. Fluorescent neurons in dorsal root and nodose ganglia were isolated using laser-capture microdissection. RNA was hybridized to Affymetrix Mouse whole genome arrays for analysis to evaluate the effects of stress and infection. RESULTS: In mice previously infected with Nb, there was no change in intestinal afferent mechanosensitivity, but there was an increase in chemosensitive responses to intraluminal hydrochloric acid when compared with control animals. Gene expression profiles in vagal but not spinal visceral sensory neurons were significantly altered in stressed Nb-infected mice. Decreased afferent responses to somatostatin receptor 2 stimulation correlated with lower expression of vagal somatostatin receptor 2 in stressed Nb-infected mice, confirming a link between molecular data and functional sequelae. CONCLUSIONS: Alterations in the intestinal brain-gut axis, in chemosensitivity but not mechanosensitivity, and through vagal rather than spinal pathways, are implicated in stress-induced postinflammatory visceral hypersensitivity.