肠易激综合征患者肠粘膜脑肠肽与肥大细胞变化及其Th1/Th2漂移的研究
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摘要
第一部分肠易激综合征患者肠粘膜脑肠肽及肥大细胞的变化
目的：探讨IBS患者肠粘膜血管活性肠肽(VIP)、降钙素基因相关肽(CGRP)和肥大细胞(MC)的变化,以及它们在IBS中的作用和临床意义。
方法：参照罗马Ⅲ诊断标准,选择腹泻型IBS (D-IBS)、便秘型IBS (C-IBS)和健康对照组各20例,每例各取回盲部、乙状结肠粘膜4块,应用免疫组织化学染色法分别检测VIP和CGRP; MC检测采用甲苯胺蓝染色法,去观察它们的阳性神经纤维表达。
结果：D-IBS、C-IBS和患者VIP、CGRP免疫阳性神经纤维及MC阳性神经纤维表达量明显高于正常对照组(P<0.01),且回盲部与乙状结肠比较无显著性差异(P>0.05),而C-IBS患者回盲部CGRP、 MC与乙状结肠比较无显著性差异。
结论：VIP、CGRP和MC可能参与了IBS的发病的病理生理过程。
第二部分肠易激综合征患者肠粘膜细胞因子Thl/Th2的漂移
目的：探讨IBS患者肠粘膜中Th1细胞因子干扰素(IFN)-γ、白细胞介素(IL)-12与Th2细胞因子IL-4、IL-10的表达情况,以阐述IBS患者肠粘膜中是否存在Th1/Th2免疫调节功能紊乱及其可能机制。
方法：按照罗马Ⅲ标准,选择60例IBS患者,其中腹泻型IBS (D-IBS)38例,其中感染后IBS (PI-IBS)20例,非感染后IBS (non-PI-IBS)18例；便秘型IBS (C-IBS)22例；健康对照20例。经结肠镜检查钳60例患者和健康对照组的升结肠、降结肠及直肠粘膜标本。采用RT-PCR和Western blot方法检测肠道各部位肠粘膜中Th1、Th2细胞因子mRNA与蛋白的表达水平。
结果：(1)D-IBS患者肠粘膜中Th1细胞因子IFN-γ、IL-12及Th2细胞因子IL-4mRNA与蛋白的表达水平较对照组差异无显著性(P>0.05),而Th2细胞因子IL-10mRNA与蛋白的表达水平显著低于对照组(P<0.05), C-IBS与健康对照比较差异无显著性(P>0.05),C-IBS与健康对照比较差异均无显著性。(2)PI-IBS患者肠粘膜中Thl细胞因子IFN-γ mRNA与蛋白的表达水平较对照组比较显著增高,差异有显著性(P<0.05)；Th2细胞因子IL-10mRNA与蛋白的表达量显著降低,差异有显著性(P<0.05)；而Thl细胞因子IL-12与Th2细胞因子IL-4mRNA与蛋白的表达水平与对照组比较,差异无显著性(P>0.05), non-PI-IBS与健康对照比较差异均无显著性。(3)各组不同部位肠粘膜内Th1、Th2细胞因子表达水平比较,差异均无显著性。
结论：(1)D-IBS患者肠粘膜中Th2抗炎细胞因子IL-10表达水平降低,存在Th1/Th2漂移,Th2反应呈弱势,相对而言Thl免疫反应占优势。(2)C-IBS患者Thl/Th2处于免疫平衡状态。(3)PI-IBS患者肠粘膜内Thl细胞因子IFN-γ表达增强,Th2细胞因子IL-10表达减弱,存在Thl/Th2漂移,明显表现为Thl免疫反应呈优势,Th2反应呈弱势。
Part I Changes of brain-gut peptide and mast cell in irritable bowel-syndrome
Objective:To investigate the changes of vasoactive intestinal polypeptide (VIP)、calcitonin gene-related peptide (CGRP) and mast cell (MC) in irritable bowel syndrome (IBS), and to study their possible roles in pathogensis.
Methods:In40patients with IBS who fulfilled the Rome Ⅲ criteria and in20non-IBS control subject, biopsy specimens taken from the mucosa of terminal ileum and recto-sigmoid junction at colouscopy were further examined using immunohistochemical staining of VIP, CGRP and MC. The results of immunohistochemisty were investigated qualitatively by color image analyzer.
Results:Significant increase of VIP, CGRP and MC were found in IBS of colon compared to the controls (P<0.01), and compared with sigmoid, there were no significantly difference in ileum. But the iluem and sigmoid compared, CGRP and MC were no significantly difference in C-IBS patients (P>0.05).
Conclusion:VIP、CGRP and MC are involved in the pathophysiological mechanism of IBS in certain ways, and their possible roles in the colon suggests the further studies may be useful in the understanding of IBS pathophysiology.
Part Ⅱ Study on the shifting of Thl/Th2balance of large intestinal mucosa in patients with irritable bowel syndrome
Objective:To investigate the expressions of Thl cytokine IFN-γ、 interleukin(IL)-12and Th2cytokine IL-4、IL-10intestinal mucosa in patients with irritable bowel syndrome(IBS). The primary of this study was to demonstrate immune mechanism underlying the activation of Thl/Th2cytokine production in colonic mucosa, so as to provide new idea for IBS in humans.
Methods:The patients with IBS were diagnosed according to Rome Ⅲ criteria. Mucosal speciments were harvested from ascending, descending colon and rectum by colonscopy in60patients with IBS and20health controls. The expressions of Thl and Th2cytokine gene expressions and protein secretion were examined by RT-PCR and Western blot respectively.
Results:(1) Compared with controls, the gene expressions and protein secretion of Thl cytokine IFN-γ、IL-12and IL-4have no significant difference. However, the expressions of Th2cytokine IL-10in diarrhea-predominant IBS (D-IBS) were decreased significantly compared with controls. In constipation predominant IBS (C-IBS) patients, the expressions of all Th1and Th2cytokine had no statistical difference compared with control.(2) The gene expression and protein secretion of IFN-γ in post infective IBS (PI-IBS) patients were increased significantly increased. The expressions of IL-4and IL-12in PI-IBS no significant difference compared with controls. However, the expressions of IL-10in PI-IBS patients were decreased significantly compared with control. The expressions of Thl and Th2cytokine in non-PI-IBS patients had no statistical difference compared with controls.(3) The expressions of Thl cytokine IFN-γ、IL-12and Th2cytokine IL-4、IL-10had no statistical difference compared with each other in all parts of gut.
Conclusion:(1) Because the expressions of Th2IL-10mRNA and protein were decreased significantly, the shift of Thl/Th2balance of colon and rectal mucosa in D-IBS patients was demonstrated along with decreased Th2activity.(2) There are Th1/Th2immune balance in C-IBS patients.(3) Because increased expression of proinflammatory cytokine Thl IFN-γ and decreased expression of anti-inflammatory cytokine Th2IL-10mRNA and protein, the shift of Thl/Th2balance of colon and rectal mucosa in PI-IBS patients was demonstrated along with increased Th1and decreased Th2immune activity.
目的：探讨IBS患者肠粘膜血管活性肠肽(VIP)、降钙素基因相关肽(CGRP)和肥大细胞(MC)的变化,以及它们在IBS中的作用和临床意义。
方法：参照罗马Ⅲ诊断标准,选择腹泻型IBS (D-IBS)、便秘型IBS (C-IBS)和健康对照组各20例,每例各取回盲部、乙状结肠粘膜4块,应用免疫组织化学染色法分别检测VIP和CGRP; MC检测采用甲苯胺蓝染色法,去观察它们的阳性神经纤维表达。
结果：D-IBS、C-IBS和患者VIP、CGRP免疫阳性神经纤维及MC阳性神经纤维表达量明显高于正常对照组(P<0.01),且回盲部与乙状结肠比较无显著性差异(P>0.05),而C-IBS患者回盲部CGRP、 MC与乙状结肠比较无显著性差异。
结论：VIP、CGRP和MC可能参与了IBS的发病的病理生理过程。
第二部分肠易激综合征患者肠粘膜细胞因子Thl/Th2的漂移
目的：探讨IBS患者肠粘膜中Th1细胞因子干扰素(IFN)-γ、白细胞介素(IL)-12与Th2细胞因子IL-4、IL-10的表达情况,以阐述IBS患者肠粘膜中是否存在Th1/Th2免疫调节功能紊乱及其可能机制。
方法：按照罗马Ⅲ标准,选择60例IBS患者,其中腹泻型IBS (D-IBS)38例,其中感染后IBS (PI-IBS)20例,非感染后IBS (non-PI-IBS)18例；便秘型IBS (C-IBS)22例；健康对照20例。经结肠镜检查钳60例患者和健康对照组的升结肠、降结肠及直肠粘膜标本。采用RT-PCR和Western blot方法检测肠道各部位肠粘膜中Th1、Th2细胞因子mRNA与蛋白的表达水平。
结果：(1)D-IBS患者肠粘膜中Th1细胞因子IFN-γ、IL-12及Th2细胞因子IL-4mRNA与蛋白的表达水平较对照组差异无显著性(P>0.05),而Th2细胞因子IL-10mRNA与蛋白的表达水平显著低于对照组(P<0.05), C-IBS与健康对照比较差异无显著性(P>0.05),C-IBS与健康对照比较差异均无显著性。(2)PI-IBS患者肠粘膜中Thl细胞因子IFN-γ mRNA与蛋白的表达水平较对照组比较显著增高,差异有显著性(P<0.05)；Th2细胞因子IL-10mRNA与蛋白的表达量显著降低,差异有显著性(P<0.05)；而Thl细胞因子IL-12与Th2细胞因子IL-4mRNA与蛋白的表达水平与对照组比较,差异无显著性(P>0.05), non-PI-IBS与健康对照比较差异均无显著性。(3)各组不同部位肠粘膜内Th1、Th2细胞因子表达水平比较,差异均无显著性。
结论：(1)D-IBS患者肠粘膜中Th2抗炎细胞因子IL-10表达水平降低,存在Th1/Th2漂移,Th2反应呈弱势,相对而言Thl免疫反应占优势。(2)C-IBS患者Thl/Th2处于免疫平衡状态。(3)PI-IBS患者肠粘膜内Thl细胞因子IFN-γ表达增强,Th2细胞因子IL-10表达减弱,存在Thl/Th2漂移,明显表现为Thl免疫反应呈优势,Th2反应呈弱势。
Part I Changes of brain-gut peptide and mast cell in irritable bowel-syndrome
Objective:To investigate the changes of vasoactive intestinal polypeptide (VIP)、calcitonin gene-related peptide (CGRP) and mast cell (MC) in irritable bowel syndrome (IBS), and to study their possible roles in pathogensis.
Methods:In40patients with IBS who fulfilled the Rome Ⅲ criteria and in20non-IBS control subject, biopsy specimens taken from the mucosa of terminal ileum and recto-sigmoid junction at colouscopy were further examined using immunohistochemical staining of VIP, CGRP and MC. The results of immunohistochemisty were investigated qualitatively by color image analyzer.
Results:Significant increase of VIP, CGRP and MC were found in IBS of colon compared to the controls (P<0.01), and compared with sigmoid, there were no significantly difference in ileum. But the iluem and sigmoid compared, CGRP and MC were no significantly difference in C-IBS patients (P>0.05).
Conclusion:VIP、CGRP and MC are involved in the pathophysiological mechanism of IBS in certain ways, and their possible roles in the colon suggests the further studies may be useful in the understanding of IBS pathophysiology.
Part Ⅱ Study on the shifting of Thl/Th2balance of large intestinal mucosa in patients with irritable bowel syndrome
Objective:To investigate the expressions of Thl cytokine IFN-γ、 interleukin(IL)-12and Th2cytokine IL-4、IL-10intestinal mucosa in patients with irritable bowel syndrome(IBS). The primary of this study was to demonstrate immune mechanism underlying the activation of Thl/Th2cytokine production in colonic mucosa, so as to provide new idea for IBS in humans.
Methods:The patients with IBS were diagnosed according to Rome Ⅲ criteria. Mucosal speciments were harvested from ascending, descending colon and rectum by colonscopy in60patients with IBS and20health controls. The expressions of Thl and Th2cytokine gene expressions and protein secretion were examined by RT-PCR and Western blot respectively.
Results:(1) Compared with controls, the gene expressions and protein secretion of Thl cytokine IFN-γ、IL-12and IL-4have no significant difference. However, the expressions of Th2cytokine IL-10in diarrhea-predominant IBS (D-IBS) were decreased significantly compared with controls. In constipation predominant IBS (C-IBS) patients, the expressions of all Th1and Th2cytokine had no statistical difference compared with control.(2) The gene expression and protein secretion of IFN-γ in post infective IBS (PI-IBS) patients were increased significantly increased. The expressions of IL-4and IL-12in PI-IBS no significant difference compared with controls. However, the expressions of IL-10in PI-IBS patients were decreased significantly compared with control. The expressions of Thl and Th2cytokine in non-PI-IBS patients had no statistical difference compared with controls.(3) The expressions of Thl cytokine IFN-γ、IL-12and Th2cytokine IL-4、IL-10had no statistical difference compared with each other in all parts of gut.
Conclusion:(1) Because the expressions of Th2IL-10mRNA and protein were decreased significantly, the shift of Thl/Th2balance of colon and rectal mucosa in D-IBS patients was demonstrated along with decreased Th2activity.(2) There are Th1/Th2immune balance in C-IBS patients.(3) Because increased expression of proinflammatory cytokine Thl IFN-γ and decreased expression of anti-inflammatory cytokine Th2IL-10mRNA and protein, the shift of Thl/Th2balance of colon and rectal mucosa in PI-IBS patients was demonstrated along with increased Th1and decreased Th2immune activity.
引文
[1]Drossman DA, Creed FH, Olden KW, et al. Psychosocial aspects of functional gastrointestinal disorders. Gut,1999,45(supple2):1125-30
[2]Harler WL. Irritable bowel syndrome. Cur Opin Gastroentol,1995,11 (2):16-21
[3]Xiong LS, Chen MH, Chen HX, et al. A population-based epidemiologic study of irritable bowel syndrome in South China:stratified randomized study by cluster sampling. Aliment pharmacol Ther,2004,19(11):1217-1224
[4]Kwan AC, Hu WH, Chan YK, et al. Prevalence of irritable bowel syndrome in Hong Kong. J Gastroenterol Hepatol,2002,17(11):1180-1186
[5]王伟岸,钱家鸣,潘国宗.结肠粘膜肥大细胞活化在肠易激综合征发病中的作用.中华消化杂志,2003,23(5)：263-266
[6]Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci,1993,38(9):1590-1595
[7]Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinal synptoms six months after bacterial gastroenteritis and risk factors for development of the irritable syndrome:postal survey of patients. BMJ,1997,314(2):779-782
[8]Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enter-endocrine cells, T lymphocytes and increased gut permeability following acute campglobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut,2000,47(6):804-811
[9]Tornblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology,2002,123(6):1972-1979
[10]O'Mahong, Mccarthy J, Kelley P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome. JAMA,2004,292 (7):852-858
[11]Longstreul GF, Thompson WG, Chey WD, et al. Functional Bowel disorders. Gastroenterology,2006,130(5):1480-1491
[12]Locke GR, Yawn BP, Wollan PC, et al. Incidence of a clinical diagnosis of the irritable bowel syndrome in a United States Population. Aliment Pharmacol Ther,2004,19(9):1025-1031
[13]Chang EY, Lu CL. Irritable bowel syndrome in the 21st century: perspectives from Asia or South-east Asia. J Gastroenterol Hepatol,2007,22(1):4-12
[14]Grlanek IM, Hays RD, Kilbourne A, et al. The impact of irritable bowel syndrome on health-related quality of life. Chin J Intl Med,2003,42 (suppl3):34-37
[15]Si JM, Chen SJ, Sun LM. An epidemiological and quality of life study of irritable bowel syndrome in Zhejiang Province. Zhonghua Nei Ke Za Zhi,2003,42(1):34-37
[16]熊智宇,陈湘,陈惠新,等.广东省社区人群肠易激综合征的流行病学研究.中华消化杂志,2004,8(4)287-289
[17]Said SI Mutt V. Polypeptide with broad biological activity:isolation from small intestine. Science,1970,169(951):1217-1218
[18]陈晓敏,张燕华,吴铁龙.肠易激综合征结肠粘膜P物质和血管活性肠肽变化的研究.实用临床医学杂志,2008,12(6)：31-33
[19]Greenwood MB, Glbson MS, Johnson AC, et al. NK1 receptor-mediated mechanisms regulate colonic hypersensitivity in the guinea pig. Pharmacol Biochem Behav,2003,74(4):1005-1013
[20]Yu D, Seitz PK, Selvanayagam P, et al. Effects of vasoactive intestinal peptide on adenosine 3'5'-monophosphate, ornithine decarboxylase,and cell growth in human colon cell line. Endocrinology,1992,131 (3):1181-1194
[21]Banan A, Zhang Y, Losurdo J, et al. Carbonylation and disassembly of the F-action cytoskeleton in oxidant induced barrier dysfunction and its prevention by epidermal growth factor and transforming growth factor alpha in a human colonic cell live. Gut,2000,46(6):830-837
[22]Zandomeneghi R, Montanari P, Serra I, et al. Role of vasoactive intestinal polypeptide(VIP) and endogenous somatostatin on the secretion of epidermal growth factor(EGF):studies on duodenal tissue cultures. Regul Pept,1990,29(2-3):75-80
[23]Banks MR, Farthing MJ, Robberecht P, et al. Antisecretory actions of a novel vasoactive intestinal polypeptide(VIP) antagonist in human and rat small intestine. Br J Pharmacol,2005,114(7):994-1001
[24]Hokari R, Lee H, Crawley sc, et al. Vasoactive intestinal peptide up regulate MUCZ intestinal muciu via CREB/AIF. Am J Physiol Gastrointest liver physiol,2005,289(167):949-959
[25]Juan Y, Liu X, Wu AW, et al. Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal N Tera2 cells. J Virol,2009,83(54):6391-6403
[26]Shi XZ, Sarna SK. Gene therapy of Cavl.2 channel with VIP and receptor agonists and antagonists:a novel approach to designing promotility and antimotility agents. Am J Physiol Gastrointest Liver Physiol,2008,295 (1):G187-G196
[27]Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[28]Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak:one-year follow-up cohort study. Gastroenterology,2005,129 (1):98-104
[29]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroentero 1,2007,42 (Suppl17):41-47
[30]Spiegel B, Schoenfeld P, Naliboff B. Systematic review:the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther,2007,26(2):183-193
[31]Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med,2004,95(5):419-426
[32]Drossman DA. The functional gastrointestinal disorders and the Rome Ⅲ process. Gastroenterology,2006,130(5):1377-1390
[33]Grider JR, Piland BE. The peristaltic reflex induced by short -chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol Gastrointest Liver Physiol,2007,292(1):G429-G437
[34]Delafoy L, Gelot A, Ardid D, et al. Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat. Gut,2006,55(7):940-945
[35]Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[36]Defilippi GC, Quera PR, Madrid SAM, et al. Rectal barostat in irritable bowel syndrome. Rev Med Chil,2006,134(12):1524-1529
[37]Park JH, Rhee PL, Kim HS, et al. Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome. Dig Dis Sci,2005,50(8):1454-1460
[38]Spaziani R, Bayati A, Redmond K, et al. Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and baroreceptor sensitivity. Neurogastroenterol Motil,2008,20(4):336-342
[39]Wilder-Smith CH, Schindler D, Lovblad K, et al. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut,2004,53(11):1595-1601
[40]Gao J, Wu X, Owyang C, et al. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats. J Physiol.2006,570(Ptl):169-183
[41]Fukudo S, Nomura T, Hongo M. Impact of corticotrophin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6):845-849
[42]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest, 2007,117(3):636-647
[43]牛庆慧,张翠萍,李炳辉,等.肠道粘膜肥大细胞和降钙素基因相关肽在肠易激综合征中的表达.世界华人消化杂志,2009,17(2)：213-217
[44]李兆坤,董文珠,邹多武,等.肠易激综合征肠基因SP,VIP,CGRP变化的研究.第二军医大学,2003,24(2)：147-151
[45]Meng J, Wang J, Lawrence G, et al. Synaptobrevin I mediates exoeytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-noticeptive potential. Journal of Cell Science,2007,120 (Pt16):2864-2874
[46]Chai Q, Arndt JW, Dong M, et al. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature,2006,444(7122):1096-1100
[47]Taylor CK, Smith DD, Hulce M, et al. Pharmacological characterization of novel alpha-calcitonin Gene-Related Peptide(CGRP) receptor peptide antagonists that are selective for human CGRP receptors. J Pharmacol Ther,2006,319(2):749-757
[48]Mallee JJ, Salvatore CA, LeBourdelles B, et al. Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists. J Biol Chem,277(16):14294-14298
[49]Harzenetter MD, Novotny AR, Garis P, et al. Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER. J Immunol,2007,179(1):607-615
[50]Buza JJ, Mori Y, Bari AM, et al. Mycobacterium avium subsp. paratuberculosis infection causes suppression of RANTES, monocyte chemoattractant protein 1, and tumor necrosis factor alpha expression in peripheral blood of experimentally infected cattle. Infect Immun,2003,71 (12):7223-7227
[51]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculations, and challenges. Gut,2001,48(1):125-131
[52]Chan YK, Herkes GK, Badcock C,et al. Alterations in cerebral potentials evoked by rectal distension in irritable bowel syndrome. Am J Gastroenterol,2001,96(8):2413-2417
[53]Talley NJ, Zinsmeister AR, Dyke CV, et al. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology, 1991,101(4):927-934
[54]Cervero F. Sensory innervation of the viscera:peripheral basis of visceral pain. Physiol Rev,1994,74 (1):95-138
[55]Posserud I, Agerforz P, Ekman R, et al. Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut,2004,53(8):1102-1108
[56]Fukudo S, Nomura T, Hongo M. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6): 845-849
[57]Sallon S, Ben-Arye E, Davidson R, et al. A novel treatment for consti-pation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula. Digestion,2002,65(3):161-171
[58]Coelho AM, Fioramonti J, Bueno L. Systemic lipopolysaccharide influences rectal sensitivity in rats:role of mast cell, cytokines, and vagus nerve. AM J Physiol Gastrointest Liver Physiol,2000,279(4):G748-790
[59]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest,2007,117 (3):636-647
[60]Collins SM. The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterol-ogy,1996,111(6):1683-1699
[61]Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Moti1,2007,19(1 Suppl): 62-88
[62]Lucas A, Cobelens PM, Kavelaars A, et al. Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission. J Neuroimmunol,2007,182(1-2):195-203
[63]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculation, and challenges. Gut,2001,48(1):125-131
[64]Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol,2006,22(1):13-17
[65]Stilwell JA, Hamlyn AN. Organic and functional disorders in gastroenterology outpatients. Lancet,1983,1(8330):938-939
[66]O'Sullivan M, Clayton N, Breslin NP, et al. Increased mucosal most cells in irritable bowel syndrome. Motil,2000,12(5):449-457
[67]Mckay DM, Perdue MH. Intestinal epithelial function:the case for immunophysiological regulation. Cells and mediators(1). Dig Dis Sci, 1993,38(8):1377-1387
[68]Gue M, Del Rio-Lacheze C, Eutameue H, et al. Stress-induced visceral hypersensitivity to rectal distension in rats:role of CRF and mast cells. Neurogastroenterol Motil,1997,9(4):271-279
[69]MacQueen G, Marshall J, Perdue M, et al. Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease Ⅱ. Science,1989,243(4887):83-85
[70]Ardizzone S, Bianchi Porro G Inflammatory bowel disease:new insights into pathogenesis and treatment. J Intern Med,2002,252 (6):475-496
[71]Bueno L, Fioramonti J. Visceral perception:inflammatory and non-inflamm-atory mediators. Gut,2002,51 (supple 1):119-123
[72]Saito YA, Schoenfeld P, Locke GR. The epidemiology of irritable bowel syndrome in North America:a systematic review. Am J Gastroenterol, 2002,97(8):1910-1915
[73]Levy RL, Jones KR, Whitehead WE,et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[74]Guthrie EA, Greed FH, Whorwell PJ,et al. Outpatients with irritable bowel syndrome:a comparison of first time and chronic attenders. Gut,1992,33(3):361-363
[75]Masarrat S, Saberi-Firoozi M, Soleimani A, et al. Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran. Eur J Gastroenterol HepatoL 1995,7(5):427-433
[76]Thumshirn M,Camilleri M,Choi MG, et al. Modulation of gastric sensory and motor functions by nitrergic and alpha2-adrenergic agents in humans. Gastroenterology,1999,116(3):573-585
[77]Philipp M,Brede M, Hein L. Physiology significance of 2-adren-ergic receptor subtype diversity90one receptor is not enough[J]. Am J Physiol Regul integr Comp Physiol,2002,134(283):R287-R295
[78]Coffin B, Azpiroz F, Guarner F, et al. Selective gastric hypersensitivity and reflex hyperactivity in functional dyspepsia. Gastroenterology,1994,107(5): 1345-1351
[79]Devroede G, Lamarche J. Functional importance of extrinsic parasympathetic innervation to the distal colon and rectum in man. Gastroenterology,1974,66(2):273-280
[80]Drossman DA,Corazziari EC,Talley NJ,Thompson WG, and White-head WE:Rome Ⅱ integrative questionnaire. In:Rome Ⅱ:The functional Gastroenterology Disorder,edited by Drossman DA,Corazziari EC, Talley NJ,Thompson WG, and Whitehead WE,Mclean VA:Degnon Associates, 2000,23(12):P691-710
[81]Drossman DA, Li Z, Toner BB, et al. Functional bowel disorders. A multicenter comparison of health status and development of illness severity index. Dig Dis Sci,1995,40(5):986-995
[82]Evans PR, Kellow JE. Physiological modulation of jejunal sensitivity in health and in irritable bowel syndrome. Am J Gastroentrol,1998, 93(11):2191-2196
[83]Stead RH, Tomioka M, Quinonez G, et al. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Sci USA,1987,84(9):2975-2979
[84]Kellow JE, Phillips SF, and Miller LJ. Dysmotility of the small intestine in irritable bowel syndrome. Gut,1988,29 (9):1236-1243
[85]Steens J, Van Der Schaar PJ, Penning C, et al. Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome. Neurogastroenterol Motil,2002,14 (3):241-247
[86]Snape WJ Jr, Wright SH, Battle WM, et al. The gastrocolic response: evidence for a neural mechanism. Gastroenterology,1979,77(6):12351240
[87]Tillisch K, Labus JS, Naliboff BD, et al. Characterization of the alternating bowel habit subtype in patients with irritable bowel syndrome. Am J Gastroenterol,2005,100(4):896-904
[88]Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut,1999,44(3):400-406
[89]Wessely S, Chalder T, Hirsh S, et al. Postinfectious fatigue:a prospective study in primary care. Lancet,1995,345(8961):1333-1338
[90]White PD, Thomas JM, Kangro HO, et al. Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet,2001,358(5):1946-1954
[91]Guthrie E, Creed F, Fernandes L, et al. Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome. Gut,2003,52(11):1616-1622
[92]Schmulson M, Lee OY, Chang L, et al. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol,1999,94(10):2929-2935
[93]Sperber AD, Carmel S, Atzmon Y, et al. Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia. Am J Gastroenterol,2000,95(4):995-998
[94]Flint AJ, Koszycki D, Bradwejn J, et al. Neurohormonal response to cholecystokinin tetrapeptide:a comparison of younger and older healthy subjects. Psychoneuroendocrinology,2000,25 (6):633-647
[95]Whitehead WE, Crowell MD, Robinson JC, et al. Effects of stressful life events on bowel symptoms:subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut,1992,33(6):825-830
[96]Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as a potential biomarker. Gastroenterology,2006,130(2):304-311
[97]D'Andrea MR, Saban MR, Gerard NP, et al. Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves. Am J physiol Regul Integr Comp Physiol,2004,288(2):491-500
[98]Barbara G, Stanghellini V, De Giorgio R,et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[99]Corsetti M, Gevers AM, Caenepeel P, et al. The role of tension receptors in colonic mechanosensitivity in humans. Gut,2004,53(12):1787-1793
[100]Bauer O and Razin E. Mast cell-nerve interaction. News physiol Sci,2000,1(15):213-218
[101]Benoist C, Mathis D. Mast cells in autoimmune disease. Nature,2002,234 (420):475-478
[102]Galli SJ, Maurer M, Lautz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol,1999,11(1):53-59
[103]Wershil BK. IX. Mast cell-deficient mice and intestinal biology. Am J physiol Gastrointest liver physiol,2000,278(3):G343-G348
[104]Van der Kleij HPM, Ma D, Wakefield D, et al. Mast cell activation and migration to lymph nodes during induction 1 receptors on mast cells induced by IL-4 and stem cell factor. J Immunol,2003,17 (171):2074-2079
[105]Kohayashi T, Miura T,Haba T, et al. An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma modle. J Immunol,2000,164(7):3855-3861
[106]Jacob C, Yang PC, Darmoul D, et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem,2005,280(36):31936-31948
[107]Galli SJ, Kalesnikoff J, Grimbaldeston MA, et al. Mast cells as "tunable" effector and immunoregulatory cells:recent advances. Annu Rev Immunol,2005,23:749-786
[108]Gebhardt T, Lorentz A, Detmer F, et al. Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor betal. Gut,2005,54(7):928-934
[109]Cao J, Cetrulo CL, Theoharides TC. Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway. Mol Pharmacol,2006,69(3):998-1006
[110]Bennett EJ, Tennant CC, Piesse C, et al. Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut,1998,43(2):256-261
[111]Michaelsson G, Kraaz W, Hagforsen E, et al. Psoriasis patients have highly increased numbers of tryptase-positive mast cells in the duodenal stroma. Br J Dermatol,1997,136(6):866-870
[112]Strobel S, Busuttil A, Ferguson A. Human intestinal mucosal mast cells: expanded population in untreated coeliac disease. Gut,1983,2(3):222-227
[113]Jakate S, Demeo M, John R, et al. Mastocytic enterocolitis:increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med, 2006,130(3):362-367
[114]Minnei F, Wetzels C, De Hertogh G, et al. Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. Virchows Arch,2006,448 (3):262-268
[115]Cherner JA, Jensen RT, Dubois A, et al. Patients with increased gastrointestinal mast cells also display similar symptoms to IBS patients. Gastrointestinal dysfunction in systemic mastocytosis. A prospective study astroenterology,1988,95 (34):657-667
[116]Siegert SI, Diebold J, Ludolph-Hauser D, et al. Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? Am J Clin Pathol,2004,122(4):565-565
[117]Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells:implications for therapy. Neurogastroenterol Motil,2006,18(1):6-17
[118]Cherner JA, Jensen RT, Dubois A, et al. Patients with increased gastrointestinal mast cells also display similar symptoms to IBS patients. Gastroenterology,1988,95(78):657-667
[119]Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology,2002,122 (7):1778-1783
[120]Talley NJ, Dennis EH, Schettler-Duncan VA, et al. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol,2003,98(11):2454-2459
[121]Stead RH, Dixon MF, Bramwell NH, et al. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology,1989,97(3): 575-585
[122]Nautiyal KM,Ribeiro AC,Praff DW, et al. Brain mast sells link the immune system to anxiety-like behavior. Proc Natl Acad U A, 2008,105(46):18053-18057
[123]Kovacs P, Herrnedi I,Wilhelm M. Mast cells modulate maintained neuronal activity in the thalamus in vivo. J Neuroimmunol,2006,171(1-2):1-7
[124]IKarashi Y, Yuzurihara M. Experimental anxiety induced by histaminergics in mast cell-deficient and congenitally normal mice. Pharmacol Biochem Behav,2002,72(1-2):473-441
[125]Addolorate G, Marsiqli L, Capristo E, et al. Anxiety and depression:A common feature of health care seeking patients with irritable bowel syndrome and food allergy. Hepatogastroenterology, 1998,45(23):1559-1564
[126]Thompson DG. IBS-the irritable of inflammation. Gastroenterology,2005,129 (1):134-141
[127]Adam B, Liebregts T, Gschossman JM, et al. Severity of mucosal inflammation as a predictor for alteration of visceral sensory function in a rat model. Pain,2006,123(1-2):179-186
[128]Haag S, Holtmann G. Change in paradigmas? From functional disorder to inflammation-associated disorder of the function activation of the mucosal immune system in irritable bowel syndrome. Z Gastroenterol,2003, 41(4):354-355
[129]Kirsch R, Riddel RH. Histopathological alteration in irritable bowel syndrome. Mod Pathol,2006,19(12):1638-1645
[130]Dunlop SP, Jeukins D, Spiller RC. Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Am J Gastroenterol,2003,98(7):1578-1583
[131]Dunlop SP, Jenkins D, Spiller RC. Age-related decline in rectal mucosal lymphocytes and mast cells. Eur J Gastroenterol Hepatol,2004,16(10): 1011-1015
[132]Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflammation in irritable bowel syndrome? Gut,2002,51 (supplel):141-144.
[133]Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system. Gastroenterology,2002,122(7):1778-1783.
[134]Mudter J,Neurath MF.Mucosal T cells:mediators or guardians of inflammatory bowel disease. Curr Opin Gastroenterol,2003,19(4):343-349
[135]Gecse K,Roka R,Ferrier L,et al. Increased faecal serine protease activity in diarrhoeic IBS patients:a colonic luminal factor impairing colonic permeability and sensitivity. Gut,2008,57 (12):591-599
[136]Baumgart,D.C.,Carding,S.R.Inflammatory bowel disease:cause and immunobiology. Lancet,2007,369 (78):1627-1640
[137]Dubovy P, Jancalek R, Klusakova I, et al. Intra-and extraneuronal changes of immuno fluorescence staining for TNF-alpha and TNFR1 in the dorsal root ganglia of rat peripheral neuropathic pain models cell. Mol. Neurobiol,2006,26:(7-8):1205-1217
[138]Bellini M, Rappelli L, Blandizzi C, et al.Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol,2003,98 (12):2705-2711
[139]Roka R, Rosztoczy A, Leveque M, et al. A pilot study of fecal serine-protease activity:a pathophysiological factor in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol,2007,5 (2):550-555
[140]Dieli F, Singh M, Spaller R, et al. Change of ThO to Thl Cell-Cytokine Profile Following Tuberculosis Chemotherapy. Scand J Immunol,2000,52(1):96-102
[141]李延青,张海燕,左秀丽,等.肠易激综合征患者肠粘膜Th1/Th2漂移的研究.中华消化杂志,2004,24(12)：728-731
[142]庞艳芹,董晶,钱伟,等.感染后肠易激综合征模型小鼠肠道组织中Th1/Th2的漂移.中华消化杂志,2010,30(1)：24-27
[143]Collins SM, Piche T, Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut,2001,49 (6):743-745
[144]Kozlov VA,Safronova IV,Kudaeva OT, et al. Contribution of Interleukin-1 to Thl- and Th2-Dependent Variants of Chronic Graft-Versus-Host Reaction. Bull Exp Biol Med,2001,132(2):769-771
[145]王俊平,侯晓华,马瑞军.腹泻型肠易激综合征患者临床特征与结肠粘膜通道蛋白8的表达.中华内科杂志,2006,45(12)：1000-1003
[146]Hogaboam CM, Vallance BA, Kumara A, et al. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest,1997,100(11):2766-2776
[147]Kuhn R, Lohler J, Rennick D, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell,1993,75(2):273-274
[148]Marchant A, Amedei A, Azaori A, et al. Polarization of PPD-specific T-cell response of patients with tuberculosis from ThO to Thl profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12. Am J Respair cell Mol Biol,2001,24(2):187-194
[149]Mukai M, Bogaki T, Kondo M, et al. Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Ann Hemaatol,2001,80(12):715-721
[150]Wataya M, Sano T, Kamikawaji N, et al. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans. J Hum genet,2001,46(4):197-206
[151]Van der Veek PP, Van den Berg M, de Koom YE, et al. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroeuterol,2005,100 (1):2510-2560
[152]Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndrome. Am J gastroenterol,2006,101(6):1295-1298
[153]Dunlop SP, Jeukin D, Spiller RC. Distinctive histological patterns of chronic inflammatory cells in rectal biopsies of patients with different clinical subtgps of IBS. Gastroenterology,2002,122 (supple1):A136
[154]Vau der Vuk PP, Van deu Berg, de Kroon YE, et al. Turner necrosis factor alpha and interleukin-10 gene polymorphism in IBS. Gastroenterology,2004, 126(suppl2):A52
[155]Clayburgh DR, Barrett TA, Tang Y, et al. Epithelial myosin light chain Kinase-dependent barrier dysfunthion mediates T cell activation-induced diarrhea in vivo. J clin Invest,2005,115 (10):2702-2705
[156]Camilleri M Atanasova E, Carlson PJ,et al. Serotonin-transporter polymorphism pharmaco-genetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology,2002,123(2):425-432
[157]Macpherson A, Khoo UY, Forgacs I, et al. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut,1996,38(3):365-375
[158]Satio YA, Zimmerman JM, Harmsen WS, et al. Irritable bowel syndrome aggregates strongly in familiesra family-based case control study. Neurogastroenterol Motil,2008,20(7):790-797
[159]Camiller M, Carlson P, Zinsmeister AR, et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastro-intestional disorders. Am J Physiol Gastrointest Liver Physiol,2009,293(3):G510-G516
[160]Lu N, Zeng H, Li ZJ. All-trans retinoic acid ameliorates trinitrobenzene sulfonic acid-induced colitis by shifting Thl to Th2 profilebai A. Interferon Cytokine Res,2010,5(28):324-316
[161]Schwarz MJ, Chiang S, Muller N, et al. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun,2001,15(4):340-370
[162]王利华,方秀才,潘国宗.肠易激综合征患者肠粘膜肥大细胞与神经纤维的关联.中华消化杂志,2003,23(6)：332-335
[163]Schwarz MJ, Chiang S, Muller N, et al. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun,2001,15(4):340-370
[164]Li Y, Wang Y, Zuo X, et al. Visceral perception thresholds after rectal thermal and pressure stimuli in irritable bowel syndrome patients. J Gastroenterol Hepatol,2004,19(2):187-191
[165]Spiller RS, Garsed K. Postifectious irritable bowel syndrome. Gastroentero-logy,2009,136(6):1979-1988
[166]Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut,1999,44(3):400-406
[167]Collins SM. A case for an immunological basis for irritable bowel syndrome. Gastroenterology,2002,122(7):2078-2080
[168]Mouteleoue I, Vasassori P, Bianocoue L, et al. Immunoregulation in gut: success and failures in human disease. Gut,2002,50(supⅢ):Ⅲ60-Ⅲ64
[169]Jenlins D, Thornleg JP, Seth R, et al. Elevated eytokines, cytotoxic product and NK cells and pathogenesis of persistent acute-ouset diarrhoea. Gut,1998,41(6):A38-39
[170]Brown DR. Mucosal protection through active intestinal secretion:neural and paracrine modulation by 5-hydroxytrytamine. Behav Brain Res,1996,73(1-2):193-197
[171]Calam J, Ghateri MA, Domin J, et al. Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy. Dig Dis Sci,1989,34(8):193-197
[172]Kuhn R, Lonler J, Rennick D, et al. Luterleukin-10 deficieut mice develop chronic enterocolitis. Cell,1993,75(2):263-274
[173]Bercik P, Wang I, Verdu EF, et al. Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology,2004,127(1):179-187
[174]Khan WI, Blennerhassett PA, Deng Y, et al. IL-12 gene transfer atters gut physiology and host immunity in nematode-infected mice. Am J physiol Gastrointest Liver Physiol,2001,281(1):G102-110
[175]Rodriguez LA, Ruigomez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis:cohort study. BMJ,1999,318(7183):565-566
[176]Fiocchi C. Inflammatory bowel disease:etiology and pathogenesis. Gastroenterology,1998,115(1):182-205
[177]孔武明,龚钧.肠易激综合征患者肠道屏障-紧密连接改变的示踪电镜观察.南方医科大学学报,2007,27(8)：1167-1169
[178]Barbasis G, Stanghellini V, Cremon C, et al. Almost all irritable bowel syndromes are post-infectious and respond to probiotics:controversial issues. Dig Dis Sci,2007,25(3):245-248
[179]Clayburgh DR, Barrett TA, Tang Y, et al. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest,2005,115(10):2702-2715
[180]Chan J, Gonsalkorale WU, Perry C, et al. IL-10 and TGF-O genotypes in irritable bowel syndromes:evidence to support an inflammalory compoment. Gastroenterology,2000,18(8):Al 31
[181]Barbare G, Wallance BA, Collins SM. Presistent intestinal neuromuscular dysfunction after acute nematode infection in mice. Gastroenterology,1997,113(4):1124-1232
[182]Mosmann TR, Cherwinski H, Bond MW, et al. Two type of murine helper T cell clone I. definition according to profiles of lympho rine activities and seereted proteins. J Immunol,1986,186(24):2343-2357
[183]Bearcoroft CP, Perrett D, Farthing MJ.5-Hydroxytryptamine release into human jejunue by cholera toxin. Gut,1996,39(4):528-531
[184]Spiller RC, Jenkins D, Thornleg JP, et al. Increased rectal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter euteritis and in post-dysenteric irritable bowel syndrome. Gut,2000,47(6):804-811
[185]Bellini M, Rappeli L, Blandizzi C, et al. Plalelet serotonin transporter in patients with diarrheu-predominant irritable bowel syndrome both before and after-treatment with albsetron. Am J Gastroentero,2003,98(12): 2705-2711
[186]Bearcoroft CP, Perrett D, Farthing MJG. Postpranelial plasma 5-hydroxytry-ptamine in irritable bowel syndrome:a pilot study. Gut,1998,42(1):42-46
[187]Groux H, O'Garre A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell respinses and prevents colitis. Nature,1997,389 (6652):737-742
[188]Rugtveit J, Brandtzaeg P, Halstensen TS, et al. Increased macrophage subset in inflammatory bowel diseases:apparent recruitment from peripheral blood monocytes. Gut,1995,35(5):669-674
[189]Weigert N, Schaffer K, Schusdziarra V, et al. Gastrin secretion from primary cultures of rabbit antral G cells:stimulation by inflammatory cytokines. Gastroenterology,1996,110(1):145-154
[190]Jones JIW, Richardson P, Hebdeu JM, et al. Value of simple screening tests for the diagnosis of chronic diarrhoea. Gut,1999,44(4):A12
[191]Spiller RC. Postinfecctious irritable bowel syndrome. Gastroenterology, 2003,124(6):1662-1671
[1]Birtwhistle RV. Irritable bowel syndrome:are complementary and alternative medicine treatments useful? Can Fam Physician,2009,55(2):1267-1289
[2]Scanu AM, Bull TJ, Cannas S, et al. Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease:common neural and immune pathogenicities. J Clin Microbi,2007,45(12):3883-3890
[3]Kalantar JS, Locke GR 3rd. Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome:a prospective study. Gut,2003,52(12):1703-1707
[4]Bengtson MB, Ronning T, Vatn MH, et al. Irritable bowel syndrome in twins genes and environment. Gut,2006,55(12):1754-1759
[5]Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[6]Park JM, Choi MG, Park JA, et al. Serotonin transporter gene polymorphism and irritable bowel syndrome. Neurogastroenterol Motil,2006, 18(11):995-1000
[7]Saito Y A, Petersen GM, Locke GR 3rd, et al. The genetics of irritable bowel syndrome. Clin Gastroenterol Hepatol,2005,3(11):1057-1065
[8]Keating E, Lemos C, Monteiro R, et al. The effect of a series of organic cations upon the plasmalemmal serotonin transporter, SERT. Life Sci,2004,76(1):103-119
[9]Jarrett ME, Kohen R, Cain KC, et al. Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome. Biol Res Nurs,2007,9(2):161-169
[10]Lea R, Whorwell PJ. The role of food intolerance in irritable bowel syndrome. Gastroenterol Clin North Am,2005,34(2):247-255
[11]Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome-etiology, prevalence and consequences. Eur J Clin Nutr,2006,60(5):667-672
[12]Kajander K, Korpela R. Clinical Studies on alleviating the symptoms of irritable bowel syndrome. Asia Pac J Clin Nutr,2006,15 (4):576-580
[13]habit in irritable bowel syndrome:a prospective, observational.1-year follow-up study(RITMO study). Aliment Pharmacol Ther, 2007,25(3):323-332
[14]Dobronte Z, Lakner L, Sarang K. Postinfectious irritable bowel syndrome. Orv Hetil,2006,147(43):2077-2080
[15]Fan YJ, Chen SJ, Yu YC, et al. Aprobiotic treatment containing lactobacillus, Bifidobacterium and Enterococcus improves IBS symptoms in an open label trial. J Zhejiang Univ Sci B,2006,7(12):987-991
[16]Colecchia A, Vestito A, La Rocca A, et al. Effect of a symbiotic preparation on the clinical manifestations of irritable bowel syndrome, constipation-variant. results of an open, uncontrolled multicenter study. Minerva Gastroenterol Dietol,2006,52(4):349-358
[17]Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak:one-year follow-up cohort study. Gastroenterology,2005,129(1):98-104
[18]O'Mahony L, Mccarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome:symptom responses and relationship to cytokine profiles. Gastroenterology,2005,128(3):541-551
[19]Lin HC. Small intestinal bacterial overgrowth:a framework for understanding irritable bowel syndrome. JAMA,2004,292(7):852-858
[20]Bercik P, Verdu EF, Collins SM. Is irritable bowel syndrome a low-grade inflammatory bowel disease? Gastroenterol Clin North Am,2005, 34(2):235-245
[21]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroenterol, 2007,42 (Suppl 17):41-47
[22]Smith JL, Bayles D. Postinfectious irritable bowel syndrome:a long-term consequence of bacterial gastroenteritis. J Food Prot,2007,70(7):1762-1769
[23]Pimentel M, Chatterjee S, Chang C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci,2008,53(4):982-989
[24]Spiller R. Serotonin, inflammation, and IBS:fitting the jigsaw together? J Pediatr Gastroenterol Nutr,2007,4 (Suppl 2):S115-S119
[25]Zou BC, Dong L, Wang Y, et al. Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome. Chin Med (Engl),2007,120(23):2069-2074
[26]Kovaces Z, Kovacs F. Depressive and anxiety symptoms, coping strategies in patients with irritable bowel syndrome and inflammatory bowel disease. Psychiatr Hung,2007,22(3):212-221
[27]Ladep NG, Obindo TJ, Audu MD, et al. Depression in patients with irritable bowel syndrome in Jos, Nigeria. World J Gastroenterol, 2006,12(48):7844-7847
[28]Cruz Ruiz MA, Ortiz Herrera RB, Muniz Jurado D, et al. Association of depression and anxiety in patients with irritable bowel syndrome. Rev Gastroenterol Mex,2007,72(1):29-33
[29]Asahin S, Hasegawa K, Tsuboi K. Depression in patients of irritable bowel syndrome. Nippon Rinsho,2006,64(8):1527-1531
[30]Faresjo A, Grodzinsky E, Johansson S, et al. Psychosocial factors at work and in every day life are associated with irritable bowel syndrome. Eur J Epidemiol,2007,22(7):473-480
[31]Xiong LS, Chen MH, Chen HX, et al. A population-based epidemiologic study of irritable bowel syndrome in South China:stratified randomized study by cluster sampling. Aliment Pharmacol Ther,2004,19(11):1217-1224
[32]Spiegel B, Schoenfeld P, Naliboff B. Systematic review:the prevalence of suicidal behavior in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmaeol Ther,2007,26(2):183-193
[33]Perona M, Benasayag R, Perello A, et al. Prevalence of functional gastrointestinal disorders in women who report domestic violence to the police. Clin Gastroenterol Hepatol,2005,3(5):436-441
[34]Hayee B, Forgacs I. Psychological approach to managing irritable bowel syndrome. BMJ,2007,334(7603):1105-1109
[35]Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med,2004,95(5):419-426
[36]Mach T. The brain-gut axis in irritable bowel syndmme-clinical aspects. Med sci Monit,2004,10(6):RA125-131
[37]Varga G, Balint A, Burghardt B, D'Amato M. Involvement of endogenous CCK and CCK1 receptors incolonic motor function. Br J Pharmacol,2004,141(8):1275-1284
[38]Banks MR, Farthing MJ, Robberecht P, et al. Antisecretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist in human and rat small intestine. Br J Pharmacol,2005,144(7):994-1001
[39]Hokari R, Lee H, Crawley SC, et al. Vasoactive intestinal peptide upregulates MUC2 intestinal muciu via CREB/ATF1. Am J Physiol Gastrointest Liver Physiol,2005,289(5):949-959
[40]Grider JR, Piland BE. The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol Gastrointestnal Liver Physiol,2007,292(1):G429-G437
[41]Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology,2006,130(5):1377-1390
[42]Delafoy L, Gelot A, Ardid D, et al. Interactive involvement of brain derived neurotrophic factor, nerve growth factor and calcitonin gene related peptide in colonic hypersensitivity in the rat. Gut,2006,55(7):940-945
[43]Corsetti M, Gevers AM, Caenepeel P, et al. The role of tension receptors in colonic mechanosensitivity in humans. Gut,2004,53(12):1787-1793
[44]Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126 (21):693-702
[45]Defilippi GC, Quera PR, Madrid SAM, et al. Rectal barostat in irritable bowel syndrome. Rev Med Chill,2006,134(12):1524-1529
[46]Park JH, Rhee PL, Kim HS, et al. Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome. Dig Dis Sci,2005,50(8):1454-1460
[47]Spaziani R, Bayati A, Redmond K, et al. Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and barereceptor sensitivity. Neurogastroenterol Motil,2008,20(4):336-342
[48]Wilder-Smith CH, Schindler D, Lovblad K, et al. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut,2004,53(11):1595-1601
[49]Gao J, Wu X, Owyang C, et al. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats. Physiol,2006,570 (Pt-1):169-183
[50]Fukudo S, Nomura T, Hongo M. Impact of corticotrophin-releasing hormone on gastrointestinal motility and adenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6):845-849
[51]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest,2007,117(3):636-647
[52]Collins SM. The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterology, 1996,111(6):1683-1699
[53]Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Moti1,2007,19(1 Suppl): 62-88
[54]Lucas A, Cobelens PM, Kavelaars A, et al. Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission. Neuroimmunol,2007,182(1-2):195-203
[55]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculation, and challenges. Gut,2001,48(1):125-131
[56]Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol,2006,22(1):13-17
[57]Harvey R, Salih S, Read A. Organic and functional disorders in gastroentero-logy outpatients. Lancet,1983,19(1):632-634
[58]Di Stefano M, Miceli E, Missanelli A, et al. Meal induced rectosigmoid tone modification:a low caloric meal accurately separates functional and organic gastrointestinal disease patients. Gut,2006,55(10):1409-1414
[59]Kellow J, Eckersley Q Jones M. Enteric and central contributions o intestinal dysmotility in irritable bowel syndrome. Dig Dis Sci,1992,2(21):68-174
[60]Ng C, Danta M, Kellow J, et al. Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol,2005,289(3):G489-G494
[61]Bearcroft CP, Perrett D, Farthing MJ. Postprandial plasma 5-hydroxy-ryptamine in diarrhoea predominant irritable bowel syndrome:a pilotstudy. Gut,1998,42(12):42-46.
[62]Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome:a randomised, placebo-controlled trial. Lancet,2000,355(9209):1035-1040
[63]Kim DY, Camilleri M. Serotonin:a mediator of the brain-gut connection. Am J Gastroenterol,2000,95(10):2698-2709
[64]Muller-Lissner S, Holtmann G, Rueegg P, et al. Tegaserod is effective in the initial and retreatment of irritable bowel syndrome with constipation. Aliment Pharmacol Ther,2005,21(1):11-20
[65]Rosztoczy A, Fioramonti J, Jarmay K, et al. Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat. Neurogastroenterol Motil,2003,15 (9):679-686
[66]Saad RT, Chev WD. Recent development in the therapy of irritable bowel disease. Expert Opin Investing Drugs,2008,17(2):117-130
[1]Longstreth GF. Thompson WG, Chey WD, et al. Funtional bowel disorders. Gastroenterology,2006,130 (34):1480-1483
[2]Bytzer P, Jones R, Mearing F. Irritable bowel syndrome:The burden andunmet needs in Europe.Dig. Liver Dis,2006,38 (12):717-723
[3]Camiller M, Andresen V. Current and novel therapeutic option for irritable bowel Syndrome management. Dig Liver Dis,2009,41(12) 854-862
[4]Guilarte M, Santos J, de Torres L, et al. Diarrhoea-predominant IBS patients show that mast cell activation and hyperplasia in the jejunum. Gut,2007, 56(2):203-209
[5]Dong WZ, Zou DW, Li ZS, et al. Study of visceral hypersensitivity in irritable bowel syndrome. Chin J Dig Dis,2004,5(3):103-109
[6]Rijnierse A, Nijkamp FP, kraneveld AD. Mast cell and nerves tickle in the tummy. Pharmacology & Therapeutics,2007,116(23):207-235
[7]Piche T, Saint-Paul MS, Dainese R, et al. Mast cell and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut,2008,57(4):468-473
[8]Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther,2009,29(7):765-773
[9]Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sic,1993,38(9):1590-1595
[10]Barbara G, stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[11]Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut,2004,53(8):1096-1101
[12]Barbara G, Stanghelini V, De Giorgio, et al. Functional gastrointestinal disorders and mast cell:implication for therapy. Neurogastroenterol Motil,2006,18(1):6-17
[13]Stead RH, Tomioka M, Quinonez G, et al. Intestinal mucosal mast cells in normal and nematode infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci U S A,1987,84(9):2975-2979
[14]Barbara G,Wang B, Stanghelini V, et al. Mast cell-dependent excitation of visceral noticeptive sensory neurons in irritable bowel syndrome. Gastroenterology,2007,132(1):26-37
[15]MacQueen G, Marshall J, Perdue M, et al. Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease Ⅱ. Science,1989,243(4887):83-85
[16]Gui X Y. Mast sells:A possible link between psychological stress enteric infection, food allergy and gut hypersensitivity in the irrita blebowel syndrome. J Gastroenterology and Hepatology,1998,13(10):980-989
[17]董文妹,邹多武,李兆申,等.肠易激综合征患者内脏高敏感性的机制研究.中华消化杂志,2004,24(1)：18-22
[18]Trau VS, Marion MA, Karatekin E, et al. Serotionin secretion by human carcinoid cells. Am Acad Sci,2004,101(4):179-188
[19]Kyosola K, Penttila O,Salaspuro M.Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterology,1997,12(3):363-367
[20]Spiller RC, Jeukins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cell, T lymphocytes and increased gut permeability following acute campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut,2007,47(6):804-811
[21]Park JH, Rhee PL, Kim G, et al. Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil,2006,18(7):539-546
[22]Dunlop SP, Jeukins D, Neal KR, et al. Relation importance of enterochromaffin cell hyperplasia,anxiety, and depression in postinfections IBS. Gastroenterology,2003,125(6):1651-1659
[23]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroentel,2007,42(Suppl17):41-47
[24]Mawe GM, Coates MD, Moses PL, et al. Review article:intestinal serotonin signalling in irritable bowel syndrome. Aliment pharmacol Ther,2006,23(8):1067-1076
[25]Gershon MD, Tack J. The serotonin signalling system:from basic understanding to drug development for functional GI disorders. Gastroenterology,2007,132(1):397-414
[26]Spiller R. Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorder:alterations in 5-HT signaling and metabolism in human disease. Neurogastroenterol Motil,2007,19(suppl 2):25-31
[27]Coates MD,Mahoney CR,Linden DR,et al. Molecular defeets in mucosal serotonin content and decreased reuptecke transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology,2004,126(7):1657-1664
[28]Growell MD, ShetEline MA, Moses DL, et al. Enterochromaffin cells and 5-HT singalling in the pathophysiology of orders of gastrointestinal function. Curr Opin Investing Drugs,2004,5(1):55-60
[29]Kyosola K, Pentlila O, Salaspuro M. Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterology,1997,12(3):363-367
[30]Miwa J,Echizen H,Matsueda K, et al. Patients with constipation-predominant irritable bowel syndrome(IBS) may have elevated serotonin concentration in colonic mucosa as compared with diarrhea-predominant patient and subjects with normal bowel habits. Digestion,2001,63 (3):188-194
[31]Borman RA, Burleigh DE. 5-HTID and 5-HT2B receptors mediate contraction of smooth muscle in human small intestine. Ann N Y Acad Sci,1997,812 (8):222-223.
[32]Wang SH, Dong L, Luo JY,et al. Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome. World J Gastroenterol,2007,13(45):6041-6047
[33]Galligan JJ, Dan H, Messori E. Singalling mechanism coupled to 5-hydroxytryptamine 4 receptor-mediated facilitation of fast synaptic transmission in the guinea-pig ileum myenteric plexus. Neurogastroeuterol Motil,2003,15(25):523-529
[34]MIURA M, LAWSON DC, CLARY EM, et al. Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-hydroxytrypamine in diarrhea predominant irritable bowel syndrome:a pilot study. Gut,1998,42(l):42
[35]CamilleriM, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biop sy specimens of patients with irritable bowel syndrome. Gastroenterology,2007,132 (1):437-441.
[36]Michel K, Zeler F, Langer R, et al. Serotonin excite neurons in the human submucous plexus via 5-HT3 receptors. Gastroenterology,2005,125(5): 1317-1326.
[37]Grundy D.5-HT System in the gut:roles in the regulation of visceral sensitivity and motor functions. Eur Rev Med Pharmacol Sci, 2008,12(Suppl 1):63-67
[38]Growell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br Jpharmacol,2004,141(8):1285-1293
[39]Breunig E, Michel K, Zeller F, et al. Histamine excites neurons in the human submucous plexus through activation of H1,H2,H3 and H4 receptors. J physio,2007,583 (Pt2):731-742
[40]Camilleri M, Atanasova E, Carlson PJ,et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology,2002,123(2):425-432
[41]Camilleri M, Andrews CN, Bharucha AE,et al. Alterations in expression of DII and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology,2007,132(1):437-441
[42]Mager L, Shileu R. Evidence for function of In molecules on gut epithelial cells in man. J Exp Med,1987,166(5):1471-1483
[43]Mudter J, Neurath MF. Mucosal T cells:mediators or guardians of inflammatory bowel disease. Curr Opin Gastroenterol,2003,19 (4):343-349
[44]Gecse K, Roka R, Ferrier L, et al. Increased faecal serine protease activity in diarrhoeic IBS patients:a colonic luminal factor impairing colonic permeability and sensitivity. Gut,2008,57 (12):591-599
[45]Baumgart DC, Carding SR. Inflammatory bowel disease:cause and immunobiology[J].Lancet,2007,369 (9573):1627-1640
[46]Dubovy P, Jancalek R, Klusakova I, et al. Intra-and extraneuronal changes of immuno fluorescence staining for TNF-alpha and TNFRl in the dorsal root ganglia of rat peripheral neuropathic pain models. Cell Mol Neurobiol,2006,26:(7-8):1205-1217
[47]Bellini M, Rappelli L, Blandizzi C, et al. Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol,200398 (12):2705-2711
[48]Roka R, Rosztoczy A, Leveque M, et al. A pilot study of fecal serine-protease activity:a pathophysiological factor in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol,2007,5 (2):550-555
[49]Dieli F, Singh M, Spaller R, et al. Change of ThO to Thl Cell-Cytokine Profile Following Tuberculosis Chemotherapy. Scand J Immunol,2000,52(1):96-102
[50]Marchant A, Amedei A, Azaori A, et al. Polarization of PPD-specific T-cell response of patients with tuberculosis from ThO to Thl profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12. Am J Respair cell Mol Biol,2001,24(2):187-194
[51]Mukai M, Bogaki T, Kondo M, et al. Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Ann Hemaatol,2001,80(12):715-721
[52]Wataya M, Sano T, Kamikawaji N, et al. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans. J Hum genet,2001,46(4):197-206
[53]Kozlov VA, Safronova IV, Kudaeva OT, et al. Contribution of Interleukin-1 to Thl- and Th2-Dependent Variants of Chronic Graft-Versus-Host Reaction. Bull Exp Biol Med,2001,132(2):769-771
[54]Sweetser SR, Linker Nord SJ, Burton DD, et al. Effects of a novel corticotrophin releasing factor receptor-1 antagonist,BMS-562086, on gastrointestinal and colonic transit and bowel habits in patients with diarrhea predominant irritable bowel syndrome(D-IBS). Gastroenterology,2008,134 (78):A548
[55]Liberegts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology,2007,132(3):913-920
[56]Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamicpituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as apotential biomarker. Gastroenterology,2006,130(2):304-311
[57]Kindt S, Van Oudenhove L, Boekaert D, et al. Immune dysfunction in patients with function gastrointestinal disorders. Neurogastroenterol Motil,2008,12 (9) [Epub ahead of print]
[58]张海燕,吴萍,李延青,等.肠易激综合征患者的免疫性等机制探讨.胃肠病学和肝脏病学杂志,2006,15(3)：285-287
[59]Uz E, Turkay C, Aytac, et al.Risk factors for irritable bowel syndrome in Turkish population:role of food allergy. J Clin Gastroenterol, 2007,4(4):380-383
[60]Saito YA, Locke Ⅲ GR, Zimmerman JM, et al. A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil,2007,19(6):465-470
[61]Li Y, Nie Y, Xie J, et al. The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and Its influence on tegaserod treatment in Chinese patients. Dig Dis Sci,2007,52(11):2942-2949
[62]Camilleri M,Kerstens R,Beyens G, et al. A double-blind, placebo-controlled trial to evaluate the safety and tolerability of prucalopride oral solution inconstipated elderly patients living in a nursing facility. Gastroenterology,2009,136(Suppl.l):240
[63]Macpherson A, Khoo UY, Forgacs I, et al. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut,1996,38(3):365-375
[64]Whorwell PJ, Mcallum M, Creed FH, et al. Non-colonic features of irritable bowel syndrome. Gut,1986,27(9):37-40
[65]Satio YA, Zimmerman JM, Harmsen WS, et al. Irritable bowel syndrome aggregates strongly in families:a family-based case control study. Neurogastroenterol Motil,2008,20(7):790-797
[66]Kim HJ, Camiller M, Carlson PJ, et al. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut,2004,53(6):829-837
[67]Yeo A, Boyd P, Lumsdens, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut,2004,53(10):1452-1458
[68]Ruiz-Pesini E, lott, Procaccio v, et al. An enhanced mitomap with a global mtDNA mutational phylogey. Nucleic Aids Research,2007,35:pD823-D828
[69]Boles RG, Adams K, Li Bu. Maternal inheritance in eyclic vomiting syndrome [J]. Am J Med Genet,2005,133A(1):71-77
[70]Camiller M, Carlson P, Zinsmeister AR, et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastro-intestional disorders. Am J Physiol Gastrointest Liver Physiol,2009,293(3):G510-G516
[71]穆标,王邦茂,刘之武,等.一氧化氮能神经调节异常在腹泻型IBS患者中的作用.中华消化杂志,2002,22(2)：88-91
[72]Kuiken SP, Klooker TK, Tytgat GN, et al. Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome. Neurogastroenterol Motil,2006,18(2):115-122
[73]Masgu K AI, Marinelli RA, Larusso NF. Water transport by epithalia of the digestive tract. Gastroenterlogy,2002,122(2):545-562
[74]Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndrome.Am J gastroenterol,2006,101 (6):1295-1298
[75]Paschos KA, Kolios G, Chatzaki E. The corticotrophin-releasing factor system in inflammatory bowel disease:prospects for new therapeutic approaches. Drug Discov,2009,14(13-14):713-720
[76]Lu N, Zeng H, Li ZJ. All-trans retinoic acid ameliorates trinitrobenzene sulfonic acid-induced colitis by shifting Thl to Th2 profilebai A. Interferon Cytokine Res,2010,5(28):324-316
[77]Fang Y, Yu S, Ellis JS. Comparison of sensitivity of Thl, Th2, and Th17 cells with Fas-mediated apoptosis. J Leukoc Biol,2010,5(23):856-876
[2]Harler WL. Irritable bowel syndrome. Cur Opin Gastroentol,1995,11 (2):16-21
[3]Xiong LS, Chen MH, Chen HX, et al. A population-based epidemiologic study of irritable bowel syndrome in South China:stratified randomized study by cluster sampling. Aliment pharmacol Ther,2004,19(11):1217-1224
[4]Kwan AC, Hu WH, Chan YK, et al. Prevalence of irritable bowel syndrome in Hong Kong. J Gastroenterol Hepatol,2002,17(11):1180-1186
[5]王伟岸,钱家鸣,潘国宗.结肠粘膜肥大细胞活化在肠易激综合征发病中的作用.中华消化杂志,2003,23(5)：263-266
[6]Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci,1993,38(9):1590-1595
[7]Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinal synptoms six months after bacterial gastroenteritis and risk factors for development of the irritable syndrome:postal survey of patients. BMJ,1997,314(2):779-782
[8]Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enter-endocrine cells, T lymphocytes and increased gut permeability following acute campglobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut,2000,47(6):804-811
[9]Tornblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology,2002,123(6):1972-1979
[10]O'Mahong, Mccarthy J, Kelley P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome. JAMA,2004,292 (7):852-858
[11]Longstreul GF, Thompson WG, Chey WD, et al. Functional Bowel disorders. Gastroenterology,2006,130(5):1480-1491
[12]Locke GR, Yawn BP, Wollan PC, et al. Incidence of a clinical diagnosis of the irritable bowel syndrome in a United States Population. Aliment Pharmacol Ther,2004,19(9):1025-1031
[13]Chang EY, Lu CL. Irritable bowel syndrome in the 21st century: perspectives from Asia or South-east Asia. J Gastroenterol Hepatol,2007,22(1):4-12
[14]Grlanek IM, Hays RD, Kilbourne A, et al. The impact of irritable bowel syndrome on health-related quality of life. Chin J Intl Med,2003,42 (suppl3):34-37
[15]Si JM, Chen SJ, Sun LM. An epidemiological and quality of life study of irritable bowel syndrome in Zhejiang Province. Zhonghua Nei Ke Za Zhi,2003,42(1):34-37
[16]熊智宇,陈湘,陈惠新,等.广东省社区人群肠易激综合征的流行病学研究.中华消化杂志,2004,8(4)287-289
[17]Said SI Mutt V. Polypeptide with broad biological activity:isolation from small intestine. Science,1970,169(951):1217-1218
[18]陈晓敏,张燕华,吴铁龙.肠易激综合征结肠粘膜P物质和血管活性肠肽变化的研究.实用临床医学杂志,2008,12(6)：31-33
[19]Greenwood MB, Glbson MS, Johnson AC, et al. NK1 receptor-mediated mechanisms regulate colonic hypersensitivity in the guinea pig. Pharmacol Biochem Behav,2003,74(4):1005-1013
[20]Yu D, Seitz PK, Selvanayagam P, et al. Effects of vasoactive intestinal peptide on adenosine 3'5'-monophosphate, ornithine decarboxylase,and cell growth in human colon cell line. Endocrinology,1992,131 (3):1181-1194
[21]Banan A, Zhang Y, Losurdo J, et al. Carbonylation and disassembly of the F-action cytoskeleton in oxidant induced barrier dysfunction and its prevention by epidermal growth factor and transforming growth factor alpha in a human colonic cell live. Gut,2000,46(6):830-837
[22]Zandomeneghi R, Montanari P, Serra I, et al. Role of vasoactive intestinal polypeptide(VIP) and endogenous somatostatin on the secretion of epidermal growth factor(EGF):studies on duodenal tissue cultures. Regul Pept,1990,29(2-3):75-80
[23]Banks MR, Farthing MJ, Robberecht P, et al. Antisecretory actions of a novel vasoactive intestinal polypeptide(VIP) antagonist in human and rat small intestine. Br J Pharmacol,2005,114(7):994-1001
[24]Hokari R, Lee H, Crawley sc, et al. Vasoactive intestinal peptide up regulate MUCZ intestinal muciu via CREB/AIF. Am J Physiol Gastrointest liver physiol,2005,289(167):949-959
[25]Juan Y, Liu X, Wu AW, et al. Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal N Tera2 cells. J Virol,2009,83(54):6391-6403
[26]Shi XZ, Sarna SK. Gene therapy of Cavl.2 channel with VIP and receptor agonists and antagonists:a novel approach to designing promotility and antimotility agents. Am J Physiol Gastrointest Liver Physiol,2008,295 (1):G187-G196
[27]Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[28]Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak:one-year follow-up cohort study. Gastroenterology,2005,129 (1):98-104
[29]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroentero 1,2007,42 (Suppl17):41-47
[30]Spiegel B, Schoenfeld P, Naliboff B. Systematic review:the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther,2007,26(2):183-193
[31]Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med,2004,95(5):419-426
[32]Drossman DA. The functional gastrointestinal disorders and the Rome Ⅲ process. Gastroenterology,2006,130(5):1377-1390
[33]Grider JR, Piland BE. The peristaltic reflex induced by short -chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol Gastrointest Liver Physiol,2007,292(1):G429-G437
[34]Delafoy L, Gelot A, Ardid D, et al. Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat. Gut,2006,55(7):940-945
[35]Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[36]Defilippi GC, Quera PR, Madrid SAM, et al. Rectal barostat in irritable bowel syndrome. Rev Med Chil,2006,134(12):1524-1529
[37]Park JH, Rhee PL, Kim HS, et al. Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome. Dig Dis Sci,2005,50(8):1454-1460
[38]Spaziani R, Bayati A, Redmond K, et al. Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and baroreceptor sensitivity. Neurogastroenterol Motil,2008,20(4):336-342
[39]Wilder-Smith CH, Schindler D, Lovblad K, et al. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut,2004,53(11):1595-1601
[40]Gao J, Wu X, Owyang C, et al. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats. J Physiol.2006,570(Ptl):169-183
[41]Fukudo S, Nomura T, Hongo M. Impact of corticotrophin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6):845-849
[42]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest, 2007,117(3):636-647
[43]牛庆慧,张翠萍,李炳辉,等.肠道粘膜肥大细胞和降钙素基因相关肽在肠易激综合征中的表达.世界华人消化杂志,2009,17(2)：213-217
[44]李兆坤,董文珠,邹多武,等.肠易激综合征肠基因SP,VIP,CGRP变化的研究.第二军医大学,2003,24(2)：147-151
[45]Meng J, Wang J, Lawrence G, et al. Synaptobrevin I mediates exoeytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-noticeptive potential. Journal of Cell Science,2007,120 (Pt16):2864-2874
[46]Chai Q, Arndt JW, Dong M, et al. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature,2006,444(7122):1096-1100
[47]Taylor CK, Smith DD, Hulce M, et al. Pharmacological characterization of novel alpha-calcitonin Gene-Related Peptide(CGRP) receptor peptide antagonists that are selective for human CGRP receptors. J Pharmacol Ther,2006,319(2):749-757
[48]Mallee JJ, Salvatore CA, LeBourdelles B, et al. Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists. J Biol Chem,277(16):14294-14298
[49]Harzenetter MD, Novotny AR, Garis P, et al. Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER. J Immunol,2007,179(1):607-615
[50]Buza JJ, Mori Y, Bari AM, et al. Mycobacterium avium subsp. paratuberculosis infection causes suppression of RANTES, monocyte chemoattractant protein 1, and tumor necrosis factor alpha expression in peripheral blood of experimentally infected cattle. Infect Immun,2003,71 (12):7223-7227
[51]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculations, and challenges. Gut,2001,48(1):125-131
[52]Chan YK, Herkes GK, Badcock C,et al. Alterations in cerebral potentials evoked by rectal distension in irritable bowel syndrome. Am J Gastroenterol,2001,96(8):2413-2417
[53]Talley NJ, Zinsmeister AR, Dyke CV, et al. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology, 1991,101(4):927-934
[54]Cervero F. Sensory innervation of the viscera:peripheral basis of visceral pain. Physiol Rev,1994,74 (1):95-138
[55]Posserud I, Agerforz P, Ekman R, et al. Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut,2004,53(8):1102-1108
[56]Fukudo S, Nomura T, Hongo M. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6): 845-849
[57]Sallon S, Ben-Arye E, Davidson R, et al. A novel treatment for consti-pation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula. Digestion,2002,65(3):161-171
[58]Coelho AM, Fioramonti J, Bueno L. Systemic lipopolysaccharide influences rectal sensitivity in rats:role of mast cell, cytokines, and vagus nerve. AM J Physiol Gastrointest Liver Physiol,2000,279(4):G748-790
[59]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest,2007,117 (3):636-647
[60]Collins SM. The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterol-ogy,1996,111(6):1683-1699
[61]Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Moti1,2007,19(1 Suppl): 62-88
[62]Lucas A, Cobelens PM, Kavelaars A, et al. Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission. J Neuroimmunol,2007,182(1-2):195-203
[63]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculation, and challenges. Gut,2001,48(1):125-131
[64]Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol,2006,22(1):13-17
[65]Stilwell JA, Hamlyn AN. Organic and functional disorders in gastroenterology outpatients. Lancet,1983,1(8330):938-939
[66]O'Sullivan M, Clayton N, Breslin NP, et al. Increased mucosal most cells in irritable bowel syndrome. Motil,2000,12(5):449-457
[67]Mckay DM, Perdue MH. Intestinal epithelial function:the case for immunophysiological regulation. Cells and mediators(1). Dig Dis Sci, 1993,38(8):1377-1387
[68]Gue M, Del Rio-Lacheze C, Eutameue H, et al. Stress-induced visceral hypersensitivity to rectal distension in rats:role of CRF and mast cells. Neurogastroenterol Motil,1997,9(4):271-279
[69]MacQueen G, Marshall J, Perdue M, et al. Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease Ⅱ. Science,1989,243(4887):83-85
[70]Ardizzone S, Bianchi Porro G Inflammatory bowel disease:new insights into pathogenesis and treatment. J Intern Med,2002,252 (6):475-496
[71]Bueno L, Fioramonti J. Visceral perception:inflammatory and non-inflamm-atory mediators. Gut,2002,51 (supple 1):119-123
[72]Saito YA, Schoenfeld P, Locke GR. The epidemiology of irritable bowel syndrome in North America:a systematic review. Am J Gastroenterol, 2002,97(8):1910-1915
[73]Levy RL, Jones KR, Whitehead WE,et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[74]Guthrie EA, Greed FH, Whorwell PJ,et al. Outpatients with irritable bowel syndrome:a comparison of first time and chronic attenders. Gut,1992,33(3):361-363
[75]Masarrat S, Saberi-Firoozi M, Soleimani A, et al. Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran. Eur J Gastroenterol HepatoL 1995,7(5):427-433
[76]Thumshirn M,Camilleri M,Choi MG, et al. Modulation of gastric sensory and motor functions by nitrergic and alpha2-adrenergic agents in humans. Gastroenterology,1999,116(3):573-585
[77]Philipp M,Brede M, Hein L. Physiology significance of 2-adren-ergic receptor subtype diversity90one receptor is not enough[J]. Am J Physiol Regul integr Comp Physiol,2002,134(283):R287-R295
[78]Coffin B, Azpiroz F, Guarner F, et al. Selective gastric hypersensitivity and reflex hyperactivity in functional dyspepsia. Gastroenterology,1994,107(5): 1345-1351
[79]Devroede G, Lamarche J. Functional importance of extrinsic parasympathetic innervation to the distal colon and rectum in man. Gastroenterology,1974,66(2):273-280
[80]Drossman DA,Corazziari EC,Talley NJ,Thompson WG, and White-head WE:Rome Ⅱ integrative questionnaire. In:Rome Ⅱ:The functional Gastroenterology Disorder,edited by Drossman DA,Corazziari EC, Talley NJ,Thompson WG, and Whitehead WE,Mclean VA:Degnon Associates, 2000,23(12):P691-710
[81]Drossman DA, Li Z, Toner BB, et al. Functional bowel disorders. A multicenter comparison of health status and development of illness severity index. Dig Dis Sci,1995,40(5):986-995
[82]Evans PR, Kellow JE. Physiological modulation of jejunal sensitivity in health and in irritable bowel syndrome. Am J Gastroentrol,1998, 93(11):2191-2196
[83]Stead RH, Tomioka M, Quinonez G, et al. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Sci USA,1987,84(9):2975-2979
[84]Kellow JE, Phillips SF, and Miller LJ. Dysmotility of the small intestine in irritable bowel syndrome. Gut,1988,29 (9):1236-1243
[85]Steens J, Van Der Schaar PJ, Penning C, et al. Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome. Neurogastroenterol Motil,2002,14 (3):241-247
[86]Snape WJ Jr, Wright SH, Battle WM, et al. The gastrocolic response: evidence for a neural mechanism. Gastroenterology,1979,77(6):12351240
[87]Tillisch K, Labus JS, Naliboff BD, et al. Characterization of the alternating bowel habit subtype in patients with irritable bowel syndrome. Am J Gastroenterol,2005,100(4):896-904
[88]Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut,1999,44(3):400-406
[89]Wessely S, Chalder T, Hirsh S, et al. Postinfectious fatigue:a prospective study in primary care. Lancet,1995,345(8961):1333-1338
[90]White PD, Thomas JM, Kangro HO, et al. Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet,2001,358(5):1946-1954
[91]Guthrie E, Creed F, Fernandes L, et al. Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome. Gut,2003,52(11):1616-1622
[92]Schmulson M, Lee OY, Chang L, et al. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol,1999,94(10):2929-2935
[93]Sperber AD, Carmel S, Atzmon Y, et al. Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia. Am J Gastroenterol,2000,95(4):995-998
[94]Flint AJ, Koszycki D, Bradwejn J, et al. Neurohormonal response to cholecystokinin tetrapeptide:a comparison of younger and older healthy subjects. Psychoneuroendocrinology,2000,25 (6):633-647
[95]Whitehead WE, Crowell MD, Robinson JC, et al. Effects of stressful life events on bowel symptoms:subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut,1992,33(6):825-830
[96]Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as a potential biomarker. Gastroenterology,2006,130(2):304-311
[97]D'Andrea MR, Saban MR, Gerard NP, et al. Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves. Am J physiol Regul Integr Comp Physiol,2004,288(2):491-500
[98]Barbara G, Stanghellini V, De Giorgio R,et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[99]Corsetti M, Gevers AM, Caenepeel P, et al. The role of tension receptors in colonic mechanosensitivity in humans. Gut,2004,53(12):1787-1793
[100]Bauer O and Razin E. Mast cell-nerve interaction. News physiol Sci,2000,1(15):213-218
[101]Benoist C, Mathis D. Mast cells in autoimmune disease. Nature,2002,234 (420):475-478
[102]Galli SJ, Maurer M, Lautz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol,1999,11(1):53-59
[103]Wershil BK. IX. Mast cell-deficient mice and intestinal biology. Am J physiol Gastrointest liver physiol,2000,278(3):G343-G348
[104]Van der Kleij HPM, Ma D, Wakefield D, et al. Mast cell activation and migration to lymph nodes during induction 1 receptors on mast cells induced by IL-4 and stem cell factor. J Immunol,2003,17 (171):2074-2079
[105]Kohayashi T, Miura T,Haba T, et al. An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma modle. J Immunol,2000,164(7):3855-3861
[106]Jacob C, Yang PC, Darmoul D, et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem,2005,280(36):31936-31948
[107]Galli SJ, Kalesnikoff J, Grimbaldeston MA, et al. Mast cells as "tunable" effector and immunoregulatory cells:recent advances. Annu Rev Immunol,2005,23:749-786
[108]Gebhardt T, Lorentz A, Detmer F, et al. Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor betal. Gut,2005,54(7):928-934
[109]Cao J, Cetrulo CL, Theoharides TC. Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway. Mol Pharmacol,2006,69(3):998-1006
[110]Bennett EJ, Tennant CC, Piesse C, et al. Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut,1998,43(2):256-261
[111]Michaelsson G, Kraaz W, Hagforsen E, et al. Psoriasis patients have highly increased numbers of tryptase-positive mast cells in the duodenal stroma. Br J Dermatol,1997,136(6):866-870
[112]Strobel S, Busuttil A, Ferguson A. Human intestinal mucosal mast cells: expanded population in untreated coeliac disease. Gut,1983,2(3):222-227
[113]Jakate S, Demeo M, John R, et al. Mastocytic enterocolitis:increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med, 2006,130(3):362-367
[114]Minnei F, Wetzels C, De Hertogh G, et al. Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. Virchows Arch,2006,448 (3):262-268
[115]Cherner JA, Jensen RT, Dubois A, et al. Patients with increased gastrointestinal mast cells also display similar symptoms to IBS patients. Gastrointestinal dysfunction in systemic mastocytosis. A prospective study astroenterology,1988,95 (34):657-667
[116]Siegert SI, Diebold J, Ludolph-Hauser D, et al. Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? Am J Clin Pathol,2004,122(4):565-565
[117]Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells:implications for therapy. Neurogastroenterol Motil,2006,18(1):6-17
[118]Cherner JA, Jensen RT, Dubois A, et al. Patients with increased gastrointestinal mast cells also display similar symptoms to IBS patients. Gastroenterology,1988,95(78):657-667
[119]Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology,2002,122 (7):1778-1783
[120]Talley NJ, Dennis EH, Schettler-Duncan VA, et al. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol,2003,98(11):2454-2459
[121]Stead RH, Dixon MF, Bramwell NH, et al. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology,1989,97(3): 575-585
[122]Nautiyal KM,Ribeiro AC,Praff DW, et al. Brain mast sells link the immune system to anxiety-like behavior. Proc Natl Acad U A, 2008,105(46):18053-18057
[123]Kovacs P, Herrnedi I,Wilhelm M. Mast cells modulate maintained neuronal activity in the thalamus in vivo. J Neuroimmunol,2006,171(1-2):1-7
[124]IKarashi Y, Yuzurihara M. Experimental anxiety induced by histaminergics in mast cell-deficient and congenitally normal mice. Pharmacol Biochem Behav,2002,72(1-2):473-441
[125]Addolorate G, Marsiqli L, Capristo E, et al. Anxiety and depression:A common feature of health care seeking patients with irritable bowel syndrome and food allergy. Hepatogastroenterology, 1998,45(23):1559-1564
[126]Thompson DG. IBS-the irritable of inflammation. Gastroenterology,2005,129 (1):134-141
[127]Adam B, Liebregts T, Gschossman JM, et al. Severity of mucosal inflammation as a predictor for alteration of visceral sensory function in a rat model. Pain,2006,123(1-2):179-186
[128]Haag S, Holtmann G. Change in paradigmas? From functional disorder to inflammation-associated disorder of the function activation of the mucosal immune system in irritable bowel syndrome. Z Gastroenterol,2003, 41(4):354-355
[129]Kirsch R, Riddel RH. Histopathological alteration in irritable bowel syndrome. Mod Pathol,2006,19(12):1638-1645
[130]Dunlop SP, Jeukins D, Spiller RC. Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Am J Gastroenterol,2003,98(7):1578-1583
[131]Dunlop SP, Jenkins D, Spiller RC. Age-related decline in rectal mucosal lymphocytes and mast cells. Eur J Gastroenterol Hepatol,2004,16(10): 1011-1015
[132]Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflammation in irritable bowel syndrome? Gut,2002,51 (supplel):141-144.
[133]Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system. Gastroenterology,2002,122(7):1778-1783.
[134]Mudter J,Neurath MF.Mucosal T cells:mediators or guardians of inflammatory bowel disease. Curr Opin Gastroenterol,2003,19(4):343-349
[135]Gecse K,Roka R,Ferrier L,et al. Increased faecal serine protease activity in diarrhoeic IBS patients:a colonic luminal factor impairing colonic permeability and sensitivity. Gut,2008,57 (12):591-599
[136]Baumgart,D.C.,Carding,S.R.Inflammatory bowel disease:cause and immunobiology. Lancet,2007,369 (78):1627-1640
[137]Dubovy P, Jancalek R, Klusakova I, et al. Intra-and extraneuronal changes of immuno fluorescence staining for TNF-alpha and TNFR1 in the dorsal root ganglia of rat peripheral neuropathic pain models cell. Mol. Neurobiol,2006,26:(7-8):1205-1217
[138]Bellini M, Rappelli L, Blandizzi C, et al.Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol,2003,98 (12):2705-2711
[139]Roka R, Rosztoczy A, Leveque M, et al. A pilot study of fecal serine-protease activity:a pathophysiological factor in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol,2007,5 (2):550-555
[140]Dieli F, Singh M, Spaller R, et al. Change of ThO to Thl Cell-Cytokine Profile Following Tuberculosis Chemotherapy. Scand J Immunol,2000,52(1):96-102
[141]李延青,张海燕,左秀丽,等.肠易激综合征患者肠粘膜Th1/Th2漂移的研究.中华消化杂志,2004,24(12)：728-731
[142]庞艳芹,董晶,钱伟,等.感染后肠易激综合征模型小鼠肠道组织中Th1/Th2的漂移.中华消化杂志,2010,30(1)：24-27
[143]Collins SM, Piche T, Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut,2001,49 (6):743-745
[144]Kozlov VA,Safronova IV,Kudaeva OT, et al. Contribution of Interleukin-1 to Thl- and Th2-Dependent Variants of Chronic Graft-Versus-Host Reaction. Bull Exp Biol Med,2001,132(2):769-771
[145]王俊平,侯晓华,马瑞军.腹泻型肠易激综合征患者临床特征与结肠粘膜通道蛋白8的表达.中华内科杂志,2006,45(12)：1000-1003
[146]Hogaboam CM, Vallance BA, Kumara A, et al. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest,1997,100(11):2766-2776
[147]Kuhn R, Lohler J, Rennick D, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell,1993,75(2):273-274
[148]Marchant A, Amedei A, Azaori A, et al. Polarization of PPD-specific T-cell response of patients with tuberculosis from ThO to Thl profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12. Am J Respair cell Mol Biol,2001,24(2):187-194
[149]Mukai M, Bogaki T, Kondo M, et al. Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Ann Hemaatol,2001,80(12):715-721
[150]Wataya M, Sano T, Kamikawaji N, et al. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans. J Hum genet,2001,46(4):197-206
[151]Van der Veek PP, Van den Berg M, de Koom YE, et al. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroeuterol,2005,100 (1):2510-2560
[152]Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndrome. Am J gastroenterol,2006,101(6):1295-1298
[153]Dunlop SP, Jeukin D, Spiller RC. Distinctive histological patterns of chronic inflammatory cells in rectal biopsies of patients with different clinical subtgps of IBS. Gastroenterology,2002,122 (supple1):A136
[154]Vau der Vuk PP, Van deu Berg, de Kroon YE, et al. Turner necrosis factor alpha and interleukin-10 gene polymorphism in IBS. Gastroenterology,2004, 126(suppl2):A52
[155]Clayburgh DR, Barrett TA, Tang Y, et al. Epithelial myosin light chain Kinase-dependent barrier dysfunthion mediates T cell activation-induced diarrhea in vivo. J clin Invest,2005,115 (10):2702-2705
[156]Camilleri M Atanasova E, Carlson PJ,et al. Serotonin-transporter polymorphism pharmaco-genetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology,2002,123(2):425-432
[157]Macpherson A, Khoo UY, Forgacs I, et al. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut,1996,38(3):365-375
[158]Satio YA, Zimmerman JM, Harmsen WS, et al. Irritable bowel syndrome aggregates strongly in familiesra family-based case control study. Neurogastroenterol Motil,2008,20(7):790-797
[159]Camiller M, Carlson P, Zinsmeister AR, et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastro-intestional disorders. Am J Physiol Gastrointest Liver Physiol,2009,293(3):G510-G516
[160]Lu N, Zeng H, Li ZJ. All-trans retinoic acid ameliorates trinitrobenzene sulfonic acid-induced colitis by shifting Thl to Th2 profilebai A. Interferon Cytokine Res,2010,5(28):324-316
[161]Schwarz MJ, Chiang S, Muller N, et al. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun,2001,15(4):340-370
[162]王利华,方秀才,潘国宗.肠易激综合征患者肠粘膜肥大细胞与神经纤维的关联.中华消化杂志,2003,23(6)：332-335
[163]Schwarz MJ, Chiang S, Muller N, et al. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun,2001,15(4):340-370
[164]Li Y, Wang Y, Zuo X, et al. Visceral perception thresholds after rectal thermal and pressure stimuli in irritable bowel syndrome patients. J Gastroenterol Hepatol,2004,19(2):187-191
[165]Spiller RS, Garsed K. Postifectious irritable bowel syndrome. Gastroentero-logy,2009,136(6):1979-1988
[166]Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut,1999,44(3):400-406
[167]Collins SM. A case for an immunological basis for irritable bowel syndrome. Gastroenterology,2002,122(7):2078-2080
[168]Mouteleoue I, Vasassori P, Bianocoue L, et al. Immunoregulation in gut: success and failures in human disease. Gut,2002,50(supⅢ):Ⅲ60-Ⅲ64
[169]Jenlins D, Thornleg JP, Seth R, et al. Elevated eytokines, cytotoxic product and NK cells and pathogenesis of persistent acute-ouset diarrhoea. Gut,1998,41(6):A38-39
[170]Brown DR. Mucosal protection through active intestinal secretion:neural and paracrine modulation by 5-hydroxytrytamine. Behav Brain Res,1996,73(1-2):193-197
[171]Calam J, Ghateri MA, Domin J, et al. Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy. Dig Dis Sci,1989,34(8):193-197
[172]Kuhn R, Lonler J, Rennick D, et al. Luterleukin-10 deficieut mice develop chronic enterocolitis. Cell,1993,75(2):263-274
[173]Bercik P, Wang I, Verdu EF, et al. Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology,2004,127(1):179-187
[174]Khan WI, Blennerhassett PA, Deng Y, et al. IL-12 gene transfer atters gut physiology and host immunity in nematode-infected mice. Am J physiol Gastrointest Liver Physiol,2001,281(1):G102-110
[175]Rodriguez LA, Ruigomez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis:cohort study. BMJ,1999,318(7183):565-566
[176]Fiocchi C. Inflammatory bowel disease:etiology and pathogenesis. Gastroenterology,1998,115(1):182-205
[177]孔武明,龚钧.肠易激综合征患者肠道屏障-紧密连接改变的示踪电镜观察.南方医科大学学报,2007,27(8)：1167-1169
[178]Barbasis G, Stanghellini V, Cremon C, et al. Almost all irritable bowel syndromes are post-infectious and respond to probiotics:controversial issues. Dig Dis Sci,2007,25(3):245-248
[179]Clayburgh DR, Barrett TA, Tang Y, et al. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest,2005,115(10):2702-2715
[180]Chan J, Gonsalkorale WU, Perry C, et al. IL-10 and TGF-O genotypes in irritable bowel syndromes:evidence to support an inflammalory compoment. Gastroenterology,2000,18(8):Al 31
[181]Barbare G, Wallance BA, Collins SM. Presistent intestinal neuromuscular dysfunction after acute nematode infection in mice. Gastroenterology,1997,113(4):1124-1232
[182]Mosmann TR, Cherwinski H, Bond MW, et al. Two type of murine helper T cell clone I. definition according to profiles of lympho rine activities and seereted proteins. J Immunol,1986,186(24):2343-2357
[183]Bearcoroft CP, Perrett D, Farthing MJ.5-Hydroxytryptamine release into human jejunue by cholera toxin. Gut,1996,39(4):528-531
[184]Spiller RC, Jenkins D, Thornleg JP, et al. Increased rectal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter euteritis and in post-dysenteric irritable bowel syndrome. Gut,2000,47(6):804-811
[185]Bellini M, Rappeli L, Blandizzi C, et al. Plalelet serotonin transporter in patients with diarrheu-predominant irritable bowel syndrome both before and after-treatment with albsetron. Am J Gastroentero,2003,98(12): 2705-2711
[186]Bearcoroft CP, Perrett D, Farthing MJG. Postpranelial plasma 5-hydroxytry-ptamine in irritable bowel syndrome:a pilot study. Gut,1998,42(1):42-46
[187]Groux H, O'Garre A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell respinses and prevents colitis. Nature,1997,389 (6652):737-742
[188]Rugtveit J, Brandtzaeg P, Halstensen TS, et al. Increased macrophage subset in inflammatory bowel diseases:apparent recruitment from peripheral blood monocytes. Gut,1995,35(5):669-674
[189]Weigert N, Schaffer K, Schusdziarra V, et al. Gastrin secretion from primary cultures of rabbit antral G cells:stimulation by inflammatory cytokines. Gastroenterology,1996,110(1):145-154
[190]Jones JIW, Richardson P, Hebdeu JM, et al. Value of simple screening tests for the diagnosis of chronic diarrhoea. Gut,1999,44(4):A12
[191]Spiller RC. Postinfecctious irritable bowel syndrome. Gastroenterology, 2003,124(6):1662-1671
[1]Birtwhistle RV. Irritable bowel syndrome:are complementary and alternative medicine treatments useful? Can Fam Physician,2009,55(2):1267-1289
[2]Scanu AM, Bull TJ, Cannas S, et al. Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease:common neural and immune pathogenicities. J Clin Microbi,2007,45(12):3883-3890
[3]Kalantar JS, Locke GR 3rd. Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome:a prospective study. Gut,2003,52(12):1703-1707
[4]Bengtson MB, Ronning T, Vatn MH, et al. Irritable bowel syndrome in twins genes and environment. Gut,2006,55(12):1754-1759
[5]Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroenterology,2001,121 (4):799-804
[6]Park JM, Choi MG, Park JA, et al. Serotonin transporter gene polymorphism and irritable bowel syndrome. Neurogastroenterol Motil,2006, 18(11):995-1000
[7]Saito Y A, Petersen GM, Locke GR 3rd, et al. The genetics of irritable bowel syndrome. Clin Gastroenterol Hepatol,2005,3(11):1057-1065
[8]Keating E, Lemos C, Monteiro R, et al. The effect of a series of organic cations upon the plasmalemmal serotonin transporter, SERT. Life Sci,2004,76(1):103-119
[9]Jarrett ME, Kohen R, Cain KC, et al. Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome. Biol Res Nurs,2007,9(2):161-169
[10]Lea R, Whorwell PJ. The role of food intolerance in irritable bowel syndrome. Gastroenterol Clin North Am,2005,34(2):247-255
[11]Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome-etiology, prevalence and consequences. Eur J Clin Nutr,2006,60(5):667-672
[12]Kajander K, Korpela R. Clinical Studies on alleviating the symptoms of irritable bowel syndrome. Asia Pac J Clin Nutr,2006,15 (4):576-580
[13]habit in irritable bowel syndrome:a prospective, observational.1-year follow-up study(RITMO study). Aliment Pharmacol Ther, 2007,25(3):323-332
[14]Dobronte Z, Lakner L, Sarang K. Postinfectious irritable bowel syndrome. Orv Hetil,2006,147(43):2077-2080
[15]Fan YJ, Chen SJ, Yu YC, et al. Aprobiotic treatment containing lactobacillus, Bifidobacterium and Enterococcus improves IBS symptoms in an open label trial. J Zhejiang Univ Sci B,2006,7(12):987-991
[16]Colecchia A, Vestito A, La Rocca A, et al. Effect of a symbiotic preparation on the clinical manifestations of irritable bowel syndrome, constipation-variant. results of an open, uncontrolled multicenter study. Minerva Gastroenterol Dietol,2006,52(4):349-358
[17]Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak:one-year follow-up cohort study. Gastroenterology,2005,129(1):98-104
[18]O'Mahony L, Mccarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome:symptom responses and relationship to cytokine profiles. Gastroenterology,2005,128(3):541-551
[19]Lin HC. Small intestinal bacterial overgrowth:a framework for understanding irritable bowel syndrome. JAMA,2004,292(7):852-858
[20]Bercik P, Verdu EF, Collins SM. Is irritable bowel syndrome a low-grade inflammatory bowel disease? Gastroenterol Clin North Am,2005, 34(2):235-245
[21]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroenterol, 2007,42 (Suppl 17):41-47
[22]Smith JL, Bayles D. Postinfectious irritable bowel syndrome:a long-term consequence of bacterial gastroenteritis. J Food Prot,2007,70(7):1762-1769
[23]Pimentel M, Chatterjee S, Chang C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci,2008,53(4):982-989
[24]Spiller R. Serotonin, inflammation, and IBS:fitting the jigsaw together? J Pediatr Gastroenterol Nutr,2007,4 (Suppl 2):S115-S119
[25]Zou BC, Dong L, Wang Y, et al. Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome. Chin Med (Engl),2007,120(23):2069-2074
[26]Kovaces Z, Kovacs F. Depressive and anxiety symptoms, coping strategies in patients with irritable bowel syndrome and inflammatory bowel disease. Psychiatr Hung,2007,22(3):212-221
[27]Ladep NG, Obindo TJ, Audu MD, et al. Depression in patients with irritable bowel syndrome in Jos, Nigeria. World J Gastroenterol, 2006,12(48):7844-7847
[28]Cruz Ruiz MA, Ortiz Herrera RB, Muniz Jurado D, et al. Association of depression and anxiety in patients with irritable bowel syndrome. Rev Gastroenterol Mex,2007,72(1):29-33
[29]Asahin S, Hasegawa K, Tsuboi K. Depression in patients of irritable bowel syndrome. Nippon Rinsho,2006,64(8):1527-1531
[30]Faresjo A, Grodzinsky E, Johansson S, et al. Psychosocial factors at work and in every day life are associated with irritable bowel syndrome. Eur J Epidemiol,2007,22(7):473-480
[31]Xiong LS, Chen MH, Chen HX, et al. A population-based epidemiologic study of irritable bowel syndrome in South China:stratified randomized study by cluster sampling. Aliment Pharmacol Ther,2004,19(11):1217-1224
[32]Spiegel B, Schoenfeld P, Naliboff B. Systematic review:the prevalence of suicidal behavior in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmaeol Ther,2007,26(2):183-193
[33]Perona M, Benasayag R, Perello A, et al. Prevalence of functional gastrointestinal disorders in women who report domestic violence to the police. Clin Gastroenterol Hepatol,2005,3(5):436-441
[34]Hayee B, Forgacs I. Psychological approach to managing irritable bowel syndrome. BMJ,2007,334(7603):1105-1109
[35]Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med,2004,95(5):419-426
[36]Mach T. The brain-gut axis in irritable bowel syndmme-clinical aspects. Med sci Monit,2004,10(6):RA125-131
[37]Varga G, Balint A, Burghardt B, D'Amato M. Involvement of endogenous CCK and CCK1 receptors incolonic motor function. Br J Pharmacol,2004,141(8):1275-1284
[38]Banks MR, Farthing MJ, Robberecht P, et al. Antisecretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist in human and rat small intestine. Br J Pharmacol,2005,144(7):994-1001
[39]Hokari R, Lee H, Crawley SC, et al. Vasoactive intestinal peptide upregulates MUC2 intestinal muciu via CREB/ATF1. Am J Physiol Gastrointest Liver Physiol,2005,289(5):949-959
[40]Grider JR, Piland BE. The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol Gastrointestnal Liver Physiol,2007,292(1):G429-G437
[41]Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology,2006,130(5):1377-1390
[42]Delafoy L, Gelot A, Ardid D, et al. Interactive involvement of brain derived neurotrophic factor, nerve growth factor and calcitonin gene related peptide in colonic hypersensitivity in the rat. Gut,2006,55(7):940-945
[43]Corsetti M, Gevers AM, Caenepeel P, et al. The role of tension receptors in colonic mechanosensitivity in humans. Gut,2004,53(12):1787-1793
[44]Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126 (21):693-702
[45]Defilippi GC, Quera PR, Madrid SAM, et al. Rectal barostat in irritable bowel syndrome. Rev Med Chill,2006,134(12):1524-1529
[46]Park JH, Rhee PL, Kim HS, et al. Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome. Dig Dis Sci,2005,50(8):1454-1460
[47]Spaziani R, Bayati A, Redmond K, et al. Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and barereceptor sensitivity. Neurogastroenterol Motil,2008,20(4):336-342
[48]Wilder-Smith CH, Schindler D, Lovblad K, et al. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut,2004,53(11):1595-1601
[49]Gao J, Wu X, Owyang C, et al. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats. Physiol,2006,570 (Pt-1):169-183
[50]Fukudo S, Nomura T, Hongo M. Impact of corticotrophin-releasing hormone on gastrointestinal motility and adenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut,1998,42(6):845-849
[51]Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest,2007,117(3):636-647
[52]Collins SM. The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterology, 1996,111(6):1683-1699
[53]Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Moti1,2007,19(1 Suppl): 62-88
[54]Lucas A, Cobelens PM, Kavelaars A, et al. Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission. Neuroimmunol,2007,182(1-2):195-203
[55]Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity:facts, speculation, and challenges. Gut,2001,48(1):125-131
[56]Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol,2006,22(1):13-17
[57]Harvey R, Salih S, Read A. Organic and functional disorders in gastroentero-logy outpatients. Lancet,1983,19(1):632-634
[58]Di Stefano M, Miceli E, Missanelli A, et al. Meal induced rectosigmoid tone modification:a low caloric meal accurately separates functional and organic gastrointestinal disease patients. Gut,2006,55(10):1409-1414
[59]Kellow J, Eckersley Q Jones M. Enteric and central contributions o intestinal dysmotility in irritable bowel syndrome. Dig Dis Sci,1992,2(21):68-174
[60]Ng C, Danta M, Kellow J, et al. Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol,2005,289(3):G489-G494
[61]Bearcroft CP, Perrett D, Farthing MJ. Postprandial plasma 5-hydroxy-ryptamine in diarrhoea predominant irritable bowel syndrome:a pilotstudy. Gut,1998,42(12):42-46.
[62]Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome:a randomised, placebo-controlled trial. Lancet,2000,355(9209):1035-1040
[63]Kim DY, Camilleri M. Serotonin:a mediator of the brain-gut connection. Am J Gastroenterol,2000,95(10):2698-2709
[64]Muller-Lissner S, Holtmann G, Rueegg P, et al. Tegaserod is effective in the initial and retreatment of irritable bowel syndrome with constipation. Aliment Pharmacol Ther,2005,21(1):11-20
[65]Rosztoczy A, Fioramonti J, Jarmay K, et al. Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat. Neurogastroenterol Motil,2003,15 (9):679-686
[66]Saad RT, Chev WD. Recent development in the therapy of irritable bowel disease. Expert Opin Investing Drugs,2008,17(2):117-130
[1]Longstreth GF. Thompson WG, Chey WD, et al. Funtional bowel disorders. Gastroenterology,2006,130 (34):1480-1483
[2]Bytzer P, Jones R, Mearing F. Irritable bowel syndrome:The burden andunmet needs in Europe.Dig. Liver Dis,2006,38 (12):717-723
[3]Camiller M, Andresen V. Current and novel therapeutic option for irritable bowel Syndrome management. Dig Liver Dis,2009,41(12) 854-862
[4]Guilarte M, Santos J, de Torres L, et al. Diarrhoea-predominant IBS patients show that mast cell activation and hyperplasia in the jejunum. Gut,2007, 56(2):203-209
[5]Dong WZ, Zou DW, Li ZS, et al. Study of visceral hypersensitivity in irritable bowel syndrome. Chin J Dig Dis,2004,5(3):103-109
[6]Rijnierse A, Nijkamp FP, kraneveld AD. Mast cell and nerves tickle in the tummy. Pharmacology & Therapeutics,2007,116(23):207-235
[7]Piche T, Saint-Paul MS, Dainese R, et al. Mast cell and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut,2008,57(4):468-473
[8]Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther,2009,29(7):765-773
[9]Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sic,1993,38(9):1590-1595
[10]Barbara G, stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology,2004,126(3):693-702
[11]Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut,2004,53(8):1096-1101
[12]Barbara G, Stanghelini V, De Giorgio, et al. Functional gastrointestinal disorders and mast cell:implication for therapy. Neurogastroenterol Motil,2006,18(1):6-17
[13]Stead RH, Tomioka M, Quinonez G, et al. Intestinal mucosal mast cells in normal and nematode infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci U S A,1987,84(9):2975-2979
[14]Barbara G,Wang B, Stanghelini V, et al. Mast cell-dependent excitation of visceral noticeptive sensory neurons in irritable bowel syndrome. Gastroenterology,2007,132(1):26-37
[15]MacQueen G, Marshall J, Perdue M, et al. Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease Ⅱ. Science,1989,243(4887):83-85
[16]Gui X Y. Mast sells:A possible link between psychological stress enteric infection, food allergy and gut hypersensitivity in the irrita blebowel syndrome. J Gastroenterology and Hepatology,1998,13(10):980-989
[17]董文妹,邹多武,李兆申,等.肠易激综合征患者内脏高敏感性的机制研究.中华消化杂志,2004,24(1)：18-22
[18]Trau VS, Marion MA, Karatekin E, et al. Serotionin secretion by human carcinoid cells. Am Acad Sci,2004,101(4):179-188
[19]Kyosola K, Penttila O,Salaspuro M.Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterology,1997,12(3):363-367
[20]Spiller RC, Jeukins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cell, T lymphocytes and increased gut permeability following acute campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut,2007,47(6):804-811
[21]Park JH, Rhee PL, Kim G, et al. Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil,2006,18(7):539-546
[22]Dunlop SP, Jeukins D, Neal KR, et al. Relation importance of enterochromaffin cell hyperplasia,anxiety, and depression in postinfections IBS. Gastroenterology,2003,125(6):1651-1659
[23]Spiller RC. Role of infection in irritable bowel syndrome. J Gastroentel,2007,42(Suppl17):41-47
[24]Mawe GM, Coates MD, Moses PL, et al. Review article:intestinal serotonin signalling in irritable bowel syndrome. Aliment pharmacol Ther,2006,23(8):1067-1076
[25]Gershon MD, Tack J. The serotonin signalling system:from basic understanding to drug development for functional GI disorders. Gastroenterology,2007,132(1):397-414
[26]Spiller R. Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorder:alterations in 5-HT signaling and metabolism in human disease. Neurogastroenterol Motil,2007,19(suppl 2):25-31
[27]Coates MD,Mahoney CR,Linden DR,et al. Molecular defeets in mucosal serotonin content and decreased reuptecke transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology,2004,126(7):1657-1664
[28]Growell MD, ShetEline MA, Moses DL, et al. Enterochromaffin cells and 5-HT singalling in the pathophysiology of orders of gastrointestinal function. Curr Opin Investing Drugs,2004,5(1):55-60
[29]Kyosola K, Pentlila O, Salaspuro M. Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterology,1997,12(3):363-367
[30]Miwa J,Echizen H,Matsueda K, et al. Patients with constipation-predominant irritable bowel syndrome(IBS) may have elevated serotonin concentration in colonic mucosa as compared with diarrhea-predominant patient and subjects with normal bowel habits. Digestion,2001,63 (3):188-194
[31]Borman RA, Burleigh DE. 5-HTID and 5-HT2B receptors mediate contraction of smooth muscle in human small intestine. Ann N Y Acad Sci,1997,812 (8):222-223.
[32]Wang SH, Dong L, Luo JY,et al. Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome. World J Gastroenterol,2007,13(45):6041-6047
[33]Galligan JJ, Dan H, Messori E. Singalling mechanism coupled to 5-hydroxytryptamine 4 receptor-mediated facilitation of fast synaptic transmission in the guinea-pig ileum myenteric plexus. Neurogastroeuterol Motil,2003,15(25):523-529
[34]MIURA M, LAWSON DC, CLARY EM, et al. Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-hydroxytrypamine in diarrhea predominant irritable bowel syndrome:a pilot study. Gut,1998,42(l):42
[35]CamilleriM, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biop sy specimens of patients with irritable bowel syndrome. Gastroenterology,2007,132 (1):437-441.
[36]Michel K, Zeler F, Langer R, et al. Serotonin excite neurons in the human submucous plexus via 5-HT3 receptors. Gastroenterology,2005,125(5): 1317-1326.
[37]Grundy D.5-HT System in the gut:roles in the regulation of visceral sensitivity and motor functions. Eur Rev Med Pharmacol Sci, 2008,12(Suppl 1):63-67
[38]Growell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br Jpharmacol,2004,141(8):1285-1293
[39]Breunig E, Michel K, Zeller F, et al. Histamine excites neurons in the human submucous plexus through activation of H1,H2,H3 and H4 receptors. J physio,2007,583 (Pt2):731-742
[40]Camilleri M, Atanasova E, Carlson PJ,et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology,2002,123(2):425-432
[41]Camilleri M, Andrews CN, Bharucha AE,et al. Alterations in expression of DII and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology,2007,132(1):437-441
[42]Mager L, Shileu R. Evidence for function of In molecules on gut epithelial cells in man. J Exp Med,1987,166(5):1471-1483
[43]Mudter J, Neurath MF. Mucosal T cells:mediators or guardians of inflammatory bowel disease. Curr Opin Gastroenterol,2003,19 (4):343-349
[44]Gecse K, Roka R, Ferrier L, et al. Increased faecal serine protease activity in diarrhoeic IBS patients:a colonic luminal factor impairing colonic permeability and sensitivity. Gut,2008,57 (12):591-599
[45]Baumgart DC, Carding SR. Inflammatory bowel disease:cause and immunobiology[J].Lancet,2007,369 (9573):1627-1640
[46]Dubovy P, Jancalek R, Klusakova I, et al. Intra-and extraneuronal changes of immuno fluorescence staining for TNF-alpha and TNFRl in the dorsal root ganglia of rat peripheral neuropathic pain models. Cell Mol Neurobiol,2006,26:(7-8):1205-1217
[47]Bellini M, Rappelli L, Blandizzi C, et al. Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol,200398 (12):2705-2711
[48]Roka R, Rosztoczy A, Leveque M, et al. A pilot study of fecal serine-protease activity:a pathophysiological factor in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol,2007,5 (2):550-555
[49]Dieli F, Singh M, Spaller R, et al. Change of ThO to Thl Cell-Cytokine Profile Following Tuberculosis Chemotherapy. Scand J Immunol,2000,52(1):96-102
[50]Marchant A, Amedei A, Azaori A, et al. Polarization of PPD-specific T-cell response of patients with tuberculosis from ThO to Thl profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12. Am J Respair cell Mol Biol,2001,24(2):187-194
[51]Mukai M, Bogaki T, Kondo M, et al. Changes in the T-helper cell 1/T-helper cell 2 balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Ann Hemaatol,2001,80(12):715-721
[52]Wataya M, Sano T, Kamikawaji N, et al. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans. J Hum genet,2001,46(4):197-206
[53]Kozlov VA, Safronova IV, Kudaeva OT, et al. Contribution of Interleukin-1 to Thl- and Th2-Dependent Variants of Chronic Graft-Versus-Host Reaction. Bull Exp Biol Med,2001,132(2):769-771
[54]Sweetser SR, Linker Nord SJ, Burton DD, et al. Effects of a novel corticotrophin releasing factor receptor-1 antagonist,BMS-562086, on gastrointestinal and colonic transit and bowel habits in patients with diarrhea predominant irritable bowel syndrome(D-IBS). Gastroenterology,2008,134 (78):A548
[55]Liberegts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology,2007,132(3):913-920
[56]Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamicpituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as apotential biomarker. Gastroenterology,2006,130(2):304-311
[57]Kindt S, Van Oudenhove L, Boekaert D, et al. Immune dysfunction in patients with function gastrointestinal disorders. Neurogastroenterol Motil,2008,12 (9) [Epub ahead of print]
[58]张海燕,吴萍,李延青,等.肠易激综合征患者的免疫性等机制探讨.胃肠病学和肝脏病学杂志,2006,15(3)：285-287
[59]Uz E, Turkay C, Aytac, et al.Risk factors for irritable bowel syndrome in Turkish population:role of food allergy. J Clin Gastroenterol, 2007,4(4):380-383
[60]Saito YA, Locke Ⅲ GR, Zimmerman JM, et al. A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil,2007,19(6):465-470
[61]Li Y, Nie Y, Xie J, et al. The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and Its influence on tegaserod treatment in Chinese patients. Dig Dis Sci,2007,52(11):2942-2949
[62]Camilleri M,Kerstens R,Beyens G, et al. A double-blind, placebo-controlled trial to evaluate the safety and tolerability of prucalopride oral solution inconstipated elderly patients living in a nursing facility. Gastroenterology,2009,136(Suppl.l):240
[63]Macpherson A, Khoo UY, Forgacs I, et al. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut,1996,38(3):365-375
[64]Whorwell PJ, Mcallum M, Creed FH, et al. Non-colonic features of irritable bowel syndrome. Gut,1986,27(9):37-40
[65]Satio YA, Zimmerman JM, Harmsen WS, et al. Irritable bowel syndrome aggregates strongly in families:a family-based case control study. Neurogastroenterol Motil,2008,20(7):790-797
[66]Kim HJ, Camiller M, Carlson PJ, et al. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut,2004,53(6):829-837
[67]Yeo A, Boyd P, Lumsdens, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut,2004,53(10):1452-1458
[68]Ruiz-Pesini E, lott, Procaccio v, et al. An enhanced mitomap with a global mtDNA mutational phylogey. Nucleic Aids Research,2007,35:pD823-D828
[69]Boles RG, Adams K, Li Bu. Maternal inheritance in eyclic vomiting syndrome [J]. Am J Med Genet,2005,133A(1):71-77
[70]Camiller M, Carlson P, Zinsmeister AR, et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastro-intestional disorders. Am J Physiol Gastrointest Liver Physiol,2009,293(3):G510-G516
[71]穆标,王邦茂,刘之武,等.一氧化氮能神经调节异常在腹泻型IBS患者中的作用.中华消化杂志,2002,22(2)：88-91
[72]Kuiken SP, Klooker TK, Tytgat GN, et al. Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome. Neurogastroenterol Motil,2006,18(2):115-122
[73]Masgu K AI, Marinelli RA, Larusso NF. Water transport by epithalia of the digestive tract. Gastroenterlogy,2002,122(2):545-562
[74]Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndrome.Am J gastroenterol,2006,101 (6):1295-1298
[75]Paschos KA, Kolios G, Chatzaki E. The corticotrophin-releasing factor system in inflammatory bowel disease:prospects for new therapeutic approaches. Drug Discov,2009,14(13-14):713-720
[76]Lu N, Zeng H, Li ZJ. All-trans retinoic acid ameliorates trinitrobenzene sulfonic acid-induced colitis by shifting Thl to Th2 profilebai A. Interferon Cytokine Res,2010,5(28):324-316
[77]Fang Y, Yu S, Ellis JS. Comparison of sensitivity of Thl, Th2, and Th17 cells with Fas-mediated apoptosis. J Leukoc Biol,2010,5(23):856-876