基于心胃相关理论组方中药对IBS模型大鼠脑肠轴CRH及肥大细胞的干预作用
摘要
肠易激综合征(IBS)是一种常见的以腹痛／腹部不适伴排便习惯改变为特征的功能性肠病,缺乏形态学和生化学改变的生物学标志。IBS的发病机制迄今仍不明确,现在普遍认为是多种因素综合作用的结果,其中心理、精神、社会和环境等因素在发病过程中起重要作用,同时受神经系统、免疫系统和内分泌系统的制约,导致肠道平滑肌运动障碍和内脏感觉异常。在此基础上,当机体受到某些诱因刺激时就会引起肠道易激和过激的功能反应,导致一系列临床症状。其症状发生的直接机制是基于肠道高敏感性和高反应性基础上的肠道运动功能异常。本文通过文献回顾了IBS的发病、致病机理、诊断治疗及肾上腺皮质激素释放因子(Corticotropin-releasing hormone, CRH)通路和肥大细胞在IBS致病作用的研究。
目的
本课题旨在通过IBS大鼠模型实验研究,探讨肠易激综合征的发生是否与肾上腺皮质激素释放因子(Corticotropin-releasing hormone, CRH)通路和肥大细胞相关。从而加深我们对肠易激综合征的发病机制的认识,并有助于解释中药康泰复方治疗肠易激综合征的作用途径及机制,为心胃相关理论治疗肠易激综合征的现代化生物学基础提供科学根据及理论支持。
方法
将育龄7天的新生SD大鼠共110只随机分出正常对照组10只,其中100只利用幼鼠母子分离加直肠刺激法复制大鼠IBS内脏高敏感性模型,造模成功后按体重随机分出模型组、中药高、中、低剂量组,和西药马来酸曲美布汀对照组各20只。给药两周后运用放射免疫法检测大鼠模型下丘脑、脑干CRH水平,免疫组化法检测IBS内脏高敏感性大鼠肠粘膜肥大细胞数目、活化状态(c-fos基因表达情况)及中药康泰复方对其影响；并与模型组及马来酸曲美布汀组进行比较。
结果
1正常大鼠与造模大鼠不同时期体重变化
用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠与正常对照组大鼠体重变化无显著性差异(P>0.05),说明本法造模不会影响大鼠的正常状态。2大鼠在清醒状态下,逐渐加压扩张肠道,观察大鼠腹部抬起与背部拱起的血压计的压力平均值,采用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠模型,在大鼠出生后第六周其内脏高敏感性显著升高(P<0.05),说明造模成功。
3、IBS内脏高敏感性大鼠经康泰胶囊治疗2周后,用药组大鼠内脏高敏感性明显降低(P<0.05),且中、高剂量治疗组已恢复到接近正常水平(P>0.05)。提示康泰胶囊对IBS模型大鼠内脏高敏感性有改善作用。
4、康泰胶囊治疗后,用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠与正常对照组大鼠体重、活动、毛发光泽无显著性差异(P>0.05),说明康泰胶囊是安全的,不存在明显的副作用。
5、与正常组相比,模型组大鼠下丘脑CRH含量明显升高,两组间比较P<0.05,差异具有统计学意义。
6、与模型组相比,西药组、中药高、中、低剂量组大鼠下丘脑CRH水平均有所降低。其中,西药组、中药康泰复方高、中剂量组与模型组相比P<0.05,差异均有统计学意义；中药低剂量组与模型组相比虽无统计学差异,但仍存在下降的趋势。
7、与正常组相比,模型组大鼠脑干CRH含量明显升高,两组间比较P<0.05,差异具有统计学意义。
8、与模型组相比,西药组、中药高、中、低剂量组大鼠脑干CRH水平均有所降低。其中,西药组、中药康泰复方高、中剂量组与模型组相比P<0.05,差异均有统计学意义；中药低剂量组与模型组相比虽无统计学差异,但仍存在下降的趋势。
9、光镜下观察c-Fos表达染色呈棕黄色,与正常组相比,模型组大鼠结肠远端肥大细胞c-fos表达水平明显升高,两组间比较P<0.05,差异具有统计学意义。
10、与模型组相比,西药组、中药高、中、低剂量组大鼠结肠远端肥大细胞c-fos基因表达水平均有所降低。其中,西药组、中药康泰复方高、中、低剂量组与模型组相比P<0.05,差异均有统计学意义；并且,中药中药康泰复方用药剂量与鼠结肠远端肥大细胞c-fos基因表达水平呈负相关。
结论
1.D-IBS大鼠脑干、下丘脑CRH含量表达的升高提示其表达改变与D-IBS的发病相关。
2.中药康泰复方是治疗IBS-D安全有效的方剂。
3.基于心胃相关理论组方的中药康泰复方能降低IBS-D高敏性大鼠脑干、下丘脑CRH含量,其作用机制可能是与影响脑肠轴CRH通路有关。
4、用科学的研究方法的出实验结果证实了周福生教授提出的“心胃相关理论”的正确性。
Irritable bowel syndrome is a common functional gastroenteropathy which is the characteristics of abdominal pain/abdominal discomfort and bowel evacuation habit, is short of change of morphology and biochemics. Its pathogenesis isnot clear so far. Now generally agreed that a lot of factors play an important role in clausing smooth muscle dyskinesia and visceral paresthesia, specifically mentality, psyche, society and circumstances, ect. This article reviews the onset, pathopoiesis, diagnosis and treatment of IBS, and relatted to gut hormones and Corticotropin-releasing hormone (CRH), MC to IBS.
OBJECTIVE
Through our animal experiments, we aim to prove that the mechanism of irritable bowel syndrome (IBS) is related with the expression of mRNA on CRH and CRH-R1in colonic mucosas. As well as deepening our understanding of the pathogenesis mechanisms of irritable bowel syndrome, it can help us to explain the pathway and mechanism of the treatment of irritable bowel syndrome with Chinese medicine Kangtai compound, and provide the scientific basis and theoretical support for the theory of the stomach treatment of irritable bowel syndrome in the modernbiology.
METHODS
A total of110Sprague-Dawley rats7D were randomly divided into normal control group and experimental group, whereas100in the experimental group. A rat model of IBS was established by Separation of mother and child plus rectal stimulation in young rats. Then the SD rats in the experimental group were randomly divided into model group、KangTai low dose group of TCM、KangTai dose group of TCM、KangTai high dose group of TCM and Trimebutine Maleate group by weight. After a treatment for two weeks, remove the thalamus, brain stem, testing CRH level and MC in Appendix.
RESULTS:
1in normal rats and model rats at different times body weight
Separation of mother and child with young rats increases visceral sensitivity to rectal stimulation in IBS rat reproduction and normal control rats no significant changes in body weight differences (P>0.05), shows the modeling of this Act does not affect the normal rats.
2rats in the awake state, the gradual expansion of intestinal pressure, the abdomen of rats raised the blood pressure with the back arched pressure, on average, increase the use of separation of mother and pups copy rectal stimulation in IBS visceral hypersensitivity in rats model, in its sixth week after birth in rat visceral hypersensitivity was significantly higher (P <0.05), shows that successful model.
3, IBS visceral hypersensitivity rats Kangtai capsule after2weeks of treatment, medication visceral hypersensitivity in rats significantly reduced (P<0.05), and middle and high dose treatment group had returned to near normal levels (P>0.05.) Tip Kangtai capsule on rat model of IBS improve the role of visceral hypersensitivity.
4, Kangtai capsule treatment, separation of mother and child with young rats increases visceral sensitivity to rectal stimulation in IBS rat reproduction and normal control group, body weight, activity, shiny hair no significant difference (P>0.05), shows Kangtai capsule is safety, there is no obvious side effects.
5, compared with the normal group, model group were significantly increased hypothalamic CRH between the two groups P<0.05, statistically significant difference.
6, compared with model group, medication group, Chinese high, medium and low-dose group hypothalamic CRH levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high dose group compared with model group, P<0.05, differences were statistically significant; medicine low dose group compared with model group although no significant difference, but there are still a downward trend
7, compared with the normal group, model group were significantly higher CRH brain stem between the two groups P<0.05, statistically significant difference.
8, compared with model group, medication group, Chinese high, medium and low-dose group brainstem CRH levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high dose group compared with model group, P<0.05, differences were statistically significant; medicine low dose group compared with model group although no significant difference, but there are still a downward trend
9, light microscopy c-Fos expression showed brown staining, compared with normal rats, the distal colon mast cell c-fos expression levels were significantly increased between the two groups P<0.05, statistical difference significance.
10, compared with model group, medication group, Chinese high, medium and low-dose group distal colon mast cells c-fos gene expression levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high, medium and low-dose group compared with model group P<0.05, differences were statistically significant; and traditional Chinese medicine traditional Chinese medicine compound dosage Conde distal colon mast cells with mouse c-fos gene expression levels were negatively correlated.
CONCLUSION:
1. D-IBS rat brain stem, hypothalamus CRH expression levels lower threshold and prompted changes in the expression of the pathogenesis of D-IBS.
(2) traditional Chinese medicine treatment of Conde IBS-D compound is safe and effective prescription.
3groups based on the theory of the heart side of the stomach medicine Conde compound can reduce IBS-D high-sensitivity in rat brain stem, hypothalamus CRH content, and its mechanism may affect the brain-gut axis with CRH pathway.
4, using scientific research methods of the experimental results confirm Professor Zhou Fusheng's "heart-related stomach theory" is correct.
目的
本课题旨在通过IBS大鼠模型实验研究,探讨肠易激综合征的发生是否与肾上腺皮质激素释放因子(Corticotropin-releasing hormone, CRH)通路和肥大细胞相关。从而加深我们对肠易激综合征的发病机制的认识,并有助于解释中药康泰复方治疗肠易激综合征的作用途径及机制,为心胃相关理论治疗肠易激综合征的现代化生物学基础提供科学根据及理论支持。
方法
将育龄7天的新生SD大鼠共110只随机分出正常对照组10只,其中100只利用幼鼠母子分离加直肠刺激法复制大鼠IBS内脏高敏感性模型,造模成功后按体重随机分出模型组、中药高、中、低剂量组,和西药马来酸曲美布汀对照组各20只。给药两周后运用放射免疫法检测大鼠模型下丘脑、脑干CRH水平,免疫组化法检测IBS内脏高敏感性大鼠肠粘膜肥大细胞数目、活化状态(c-fos基因表达情况)及中药康泰复方对其影响；并与模型组及马来酸曲美布汀组进行比较。
结果
1正常大鼠与造模大鼠不同时期体重变化
用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠与正常对照组大鼠体重变化无显著性差异(P>0.05),说明本法造模不会影响大鼠的正常状态。2大鼠在清醒状态下,逐渐加压扩张肠道,观察大鼠腹部抬起与背部拱起的血压计的压力平均值,采用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠模型,在大鼠出生后第六周其内脏高敏感性显著升高(P<0.05),说明造模成功。
3、IBS内脏高敏感性大鼠经康泰胶囊治疗2周后,用药组大鼠内脏高敏感性明显降低(P<0.05),且中、高剂量治疗组已恢复到接近正常水平(P>0.05)。提示康泰胶囊对IBS模型大鼠内脏高敏感性有改善作用。
4、康泰胶囊治疗后,用幼鼠母子分离加直肠刺激法复制内脏高敏感性IBS大鼠与正常对照组大鼠体重、活动、毛发光泽无显著性差异(P>0.05),说明康泰胶囊是安全的,不存在明显的副作用。
5、与正常组相比,模型组大鼠下丘脑CRH含量明显升高,两组间比较P<0.05,差异具有统计学意义。
6、与模型组相比,西药组、中药高、中、低剂量组大鼠下丘脑CRH水平均有所降低。其中,西药组、中药康泰复方高、中剂量组与模型组相比P<0.05,差异均有统计学意义；中药低剂量组与模型组相比虽无统计学差异,但仍存在下降的趋势。
7、与正常组相比,模型组大鼠脑干CRH含量明显升高,两组间比较P<0.05,差异具有统计学意义。
8、与模型组相比,西药组、中药高、中、低剂量组大鼠脑干CRH水平均有所降低。其中,西药组、中药康泰复方高、中剂量组与模型组相比P<0.05,差异均有统计学意义；中药低剂量组与模型组相比虽无统计学差异,但仍存在下降的趋势。
9、光镜下观察c-Fos表达染色呈棕黄色,与正常组相比,模型组大鼠结肠远端肥大细胞c-fos表达水平明显升高,两组间比较P<0.05,差异具有统计学意义。
10、与模型组相比,西药组、中药高、中、低剂量组大鼠结肠远端肥大细胞c-fos基因表达水平均有所降低。其中,西药组、中药康泰复方高、中、低剂量组与模型组相比P<0.05,差异均有统计学意义；并且,中药中药康泰复方用药剂量与鼠结肠远端肥大细胞c-fos基因表达水平呈负相关。
结论
1.D-IBS大鼠脑干、下丘脑CRH含量表达的升高提示其表达改变与D-IBS的发病相关。
2.中药康泰复方是治疗IBS-D安全有效的方剂。
3.基于心胃相关理论组方的中药康泰复方能降低IBS-D高敏性大鼠脑干、下丘脑CRH含量,其作用机制可能是与影响脑肠轴CRH通路有关。
4、用科学的研究方法的出实验结果证实了周福生教授提出的“心胃相关理论”的正确性。
Irritable bowel syndrome is a common functional gastroenteropathy which is the characteristics of abdominal pain/abdominal discomfort and bowel evacuation habit, is short of change of morphology and biochemics. Its pathogenesis isnot clear so far. Now generally agreed that a lot of factors play an important role in clausing smooth muscle dyskinesia and visceral paresthesia, specifically mentality, psyche, society and circumstances, ect. This article reviews the onset, pathopoiesis, diagnosis and treatment of IBS, and relatted to gut hormones and Corticotropin-releasing hormone (CRH), MC to IBS.
OBJECTIVE
Through our animal experiments, we aim to prove that the mechanism of irritable bowel syndrome (IBS) is related with the expression of mRNA on CRH and CRH-R1in colonic mucosas. As well as deepening our understanding of the pathogenesis mechanisms of irritable bowel syndrome, it can help us to explain the pathway and mechanism of the treatment of irritable bowel syndrome with Chinese medicine Kangtai compound, and provide the scientific basis and theoretical support for the theory of the stomach treatment of irritable bowel syndrome in the modernbiology.
METHODS
A total of110Sprague-Dawley rats7D were randomly divided into normal control group and experimental group, whereas100in the experimental group. A rat model of IBS was established by Separation of mother and child plus rectal stimulation in young rats. Then the SD rats in the experimental group were randomly divided into model group、KangTai low dose group of TCM、KangTai dose group of TCM、KangTai high dose group of TCM and Trimebutine Maleate group by weight. After a treatment for two weeks, remove the thalamus, brain stem, testing CRH level and MC in Appendix.
RESULTS:
1in normal rats and model rats at different times body weight
Separation of mother and child with young rats increases visceral sensitivity to rectal stimulation in IBS rat reproduction and normal control rats no significant changes in body weight differences (P>0.05), shows the modeling of this Act does not affect the normal rats.
2rats in the awake state, the gradual expansion of intestinal pressure, the abdomen of rats raised the blood pressure with the back arched pressure, on average, increase the use of separation of mother and pups copy rectal stimulation in IBS visceral hypersensitivity in rats model, in its sixth week after birth in rat visceral hypersensitivity was significantly higher (P <0.05), shows that successful model.
3, IBS visceral hypersensitivity rats Kangtai capsule after2weeks of treatment, medication visceral hypersensitivity in rats significantly reduced (P<0.05), and middle and high dose treatment group had returned to near normal levels (P>0.05.) Tip Kangtai capsule on rat model of IBS improve the role of visceral hypersensitivity.
4, Kangtai capsule treatment, separation of mother and child with young rats increases visceral sensitivity to rectal stimulation in IBS rat reproduction and normal control group, body weight, activity, shiny hair no significant difference (P>0.05), shows Kangtai capsule is safety, there is no obvious side effects.
5, compared with the normal group, model group were significantly increased hypothalamic CRH between the two groups P<0.05, statistically significant difference.
6, compared with model group, medication group, Chinese high, medium and low-dose group hypothalamic CRH levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high dose group compared with model group, P<0.05, differences were statistically significant; medicine low dose group compared with model group although no significant difference, but there are still a downward trend
7, compared with the normal group, model group were significantly higher CRH brain stem between the two groups P<0.05, statistically significant difference.
8, compared with model group, medication group, Chinese high, medium and low-dose group brainstem CRH levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high dose group compared with model group, P<0.05, differences were statistically significant; medicine low dose group compared with model group although no significant difference, but there are still a downward trend
9, light microscopy c-Fos expression showed brown staining, compared with normal rats, the distal colon mast cell c-fos expression levels were significantly increased between the two groups P<0.05, statistical difference significance.
10, compared with model group, medication group, Chinese high, medium and low-dose group distal colon mast cells c-fos gene expression levels were decreased. Among them, the western medicine group, traditional Chinese medicine compound Conde high, medium and low-dose group compared with model group P<0.05, differences were statistically significant; and traditional Chinese medicine traditional Chinese medicine compound dosage Conde distal colon mast cells with mouse c-fos gene expression levels were negatively correlated.
CONCLUSION:
1. D-IBS rat brain stem, hypothalamus CRH expression levels lower threshold and prompted changes in the expression of the pathogenesis of D-IBS.
(2) traditional Chinese medicine treatment of Conde IBS-D compound is safe and effective prescription.
3groups based on the theory of the heart side of the stomach medicine Conde compound can reduce IBS-D high-sensitivity in rat brain stem, hypothalamus CRH content, and its mechanism may affect the brain-gut axis with CRH pathway.
4, using scientific research methods of the experimental results confirm Professor Zhou Fusheng's "heart-related stomach theory" is correct.
引文
[1]Talley NJ, Spiller R. Irritable bowel syndrome:a little understood organic bowel disease Lancet,2002,360:555-64.
[2]Garnett WR. Clinical consult:management of irritable bowel syndrome [online]. J Am Soc Consultant Pharm,1999,14 (Suppl 8).
[3]Frauke Musial, Winfried Hauser, Jost Langhorst. Psychophysiology of visceral pain in IBS and health. Journal of Psychosomatic Research,2008,64:589-597.
[4]Garakani, Amir, Win, et al. Comorbidity of irritable bowel syndrome in psychiatric patients:A Review[J]. American Journal of Therapeutics,2003,10(1):61
[5]崔桂淑.肠易激综合征发病机制的研究现状及进展[J].中国煤炭工业医学杂志,2002,5(9)：865
[6]邹多武,董文珠,李兆申,等.肠易激综合征患者内脏高敏感性与肥大细胞的关系[J].第一军医大学学报,2003,24：143
[7]项柏康.重视肠易激综合征发病机理的研究及中医药治疗[J].浙江中医学院学报,2000,24：15.
[8]Small PK, London MA, Han CM, et al.Large scale ambulatory study of post prandial jejunal motility in irritable bowel syndrome[J]. Scand J Gastroenterol,1997,32:39
[9]King TS, Elia M, Hunter J. Evidence for abnormal fermentation in the irritable bowel syndrome[J]. Lancet,1998,352:1187
[10]Distefano M, Strochi A, Malservise S, et al. Non-absorbable antibiotics for managing intestinal gas production and gas related symptoms[J]. Alimentpharmacol Ther,2000, 14:1001
[11]李定国,李兆东.肠易激综合征研究现状与展望[J].中华消化杂志,2001,21(2) 69
[12]Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factor s for development of t he irritable bowel syndrome:postal survey of patients[J]. BMJ,1997,314:779-782. [13]Dobronte Z, Lakner L, Sarang K. Postinfectious irritable bowel syndrome[J]. Orv Hetil,2006,147:2077-2080.
[14]Ji S, Park H, Lee D, et al. Postinfectious irritable bowel syndrome in patients with Shigella infection[J]. J Gastroenterol Hepatol,2005,20:381-386.
[15]Barbara G, Vallance BA, Collins SM. Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice[J].Gast roenterology,1997,113:1224-1232.
[16]Gerards C, Leodolter A, Glasbrenner B, et al. H. Pylori infection and visceral hypersensitivity in patients wit h irritable bowel syndrome[J]. Dig Dis,2001,19: 170-173.
[17]Vergnolle N, Renaux B, Hollenberg MD, et al. Role of rat mast cell protease-2 in intestinal transport and barriar function. Gastroenterology,1998,114 (suppl):A674.
[18]Hebden JM, Erah PO,Blackshaw PE, et al. Increased small bowel but not colonic permeability in pos-infectious irritable bowel syndrome[J]. Gastroenterology, 1998,114(suppl):A429.
[19]范红,万萍,何旭,等.胆囊及奥狄氏括约肌功能紊乱与IBS的相关性研究[J].中国肛肠病杂志,2000,20(7)：11
[20]贾勇,王巧民,戴海明,等.肠易激综合征T淋巴细胞亚群变化及其意义[J].临床消化杂志,2002,14(2)：60-61
[21]张茹,张秀华,孙孟类,等.肠易激综合征血清中工L-8和TNF-a的变化及意义[J].中华腹部疾病杂志,2004,4(1)：7-10
[22]Stead RH. Innervation of mucosal immune cells in the gastrointestinal tract[J]. Reg Immunol,1992,4 (2):91-99
[23]Oliver MR, Tan DT, Scott RB et al, Colonic motor response to IGE-mediated mast cell degranul. ation in the Hooded-Lister rat[J]. Neurogastroenterol Motil,1996,8 (2):121-130
[24]Wood JD. Khin J.Neurotransmission at the interface of sympathetic and enteric divisions of the autonomic nervous system[J]. physiol,1999;42 (4):201-210
[25]邹多武,董文珠,李兆申,等.肠易激综合征患者内脏高敏感性与肥大细胞的关系[J].第一军医大学学报,2003,24(2)：143-146
[26]李青,王梅艳,吕国苹,等.腹部冷刺激对肠易激综合征患者内脏感觉闭值的影响[J]..胃肠病学和肝病学杂志,2002,11(4)：339-341
[27]Hasler A,Koursarakos P, Patsopoulos of irritable bowel syndromeinpatients with.increased prevalence bronchial asthma[J]. RespirMed.2003,97(1):75-79
[28]张正利,蔡淦.肠易激综合征中医论治溯源.中国中医基础医学杂志,2001,7(7)：48-50
[29]谢建群,李国霞,陆雄等.疏肝健脾汤对肠易激综合征血浆胃动素的调节作用.上海中医药杂志,2001,35(6)：13-14
[30]Zhaoxiang Bian, Ph. D, Taixtang WU, M. D, Liang Liu, Ph. D. et al. Effectiveness of the Chinese Herbal Formula TongXieYaoFang for Irritable Bowel Syndrome:A Systematic Review. THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE.2006,12(4):401-407
[31]周福生,吴文江,张庆宏.胃肠功能性疾病证型分布的统计分析.中华国际医学杂志,2002,2(5)：438-442
[32]张庆宏,周福生.析“心胃相关”.云南中医学院学报,2001,24(2)：38
[33]周福生,程宏辉,祝淑贞.心胃相关理论及临床应用,浙江中医学院学报,2004,28(2)：7-8
[35]黄适,林寿宁,雷立民,等.安肠汤结肠水疗对腹泻型肠易激综合征患者IL-1 B h和IL-10 的影响.现代中西医结合杂志.2010,19(1)：11-12.
[36]尹丽菊.二术汤加味治疗腹泻型肠易激综合症50例.吉林中医药.2002,3(22)：16.
[37]申亚东,张峰.加味逍遥散治疗腹泻型肠易激综合征85例.河南中医药学刊.2000,6(15)：37-38.
[38]邓革强,唐清珠.柔肝抑肠汤治疗腹泻型肠易激综合症37例.中医研究.2006,11(19)：30-31.
[39]温庆华,袁泉英.加味半夏泻心汤治疗肠易激综合征86例.江西中医药.2009,8(40)：33.
[40]岳妍,王文仲,杨强,等.蒺藜汤治疗腹泻型肠易激综合征.中国中医药信息杂志.2004,5(11)：447.
[41]陈玲.疏肝理肠汤治疗肠易激综合症48例.湖南中医杂志.2004,2(20)：39.
[42]黄小雄等.痛泻要方合乌梅丸治疗肠易激综合征30例体会.现代中医药.2004,5：13-14.
[43]杨军.小建中汤加减治疗肠易激综合征36例.陕西中医.2005,9(26)：920.
[44]周福生,吴文江,黄志新.顺激合剂治疗肠易激综合征综合疗效观察.广州中医药大学学报.2002,4(19)：269-271.
[45]刘炳炎.自拟久泻散治疗肠易激综合征116例.中华现代中西医杂志.2005,3(3)：248-249.
[46]王刚,李延谦,王蕾等.痛泻宁颗粒治疗腹泻型肠易激综合征(肝气乘脾证)的随机双盲安慰剂对照试验.中国询证医学杂志.2006,2(6)：84-89.
[47]王兴纬,卞晓云.王氏保赤丸联合心理治疗肠易激综合征.江苏医药.2007,8(33)：856-857.
[48]云雅卿,王红霞.加味二至丸治疗便秘型肠易激综合征验案举隅.中医临床研究.2010,10(2)：29.
[49]孙洁.健脾调肝汤治疗肠易激综合征50例.陕西中医.2005,9(26)：918-919.
[50]黄惠凤,季顺祥.固肠止泻丸联合思密达治疗腹泻型肠易激综合征疗效观察.使用中西医结合临床.2006,6(6)：11-12.
[51]左新红.中西医结合治疗腹泻型肠易激综合症32例.中医研究.2007,11(20)：34-35.
[52]赵文召,高春芳.小建中汤联合保健乳治疗肠易激综合征的临床观察.临床军医杂志.2010,3(38)：406-409.
[53]张国忠,郭丽芳,刘彦岭,等.按摩治疗便秘型肠易激综合征疗效观察.现代中西医结合杂志.2010,19(13)：1584-1585.
[54]刘慧荣,华雪桂,杨允,等.腹泻型IBS结肠黏膜5-HT表达及隔药灸治疗的临床研究.辽宁中医杂志.2006,8(33)：984-985.
[55]郭光丽,鲍虎豹,张亚滨.温针灸治疗腹泻型肠易激综合征疗效观察.现代中西医结合杂志.2010,19(16)：1998-1999.
[56]梁谊深,张越,冯金娟.太极拳运动结合穴位埋线治疗便秘型肠易激综合征疗效观察.湖北中医杂志.2010,10(32)：50-51.
[57]张志杰,张越,谢胜,等.药穴指针疗法治疗腹泻型肠易激综合征35例.陕西中医.2010,12(31)：1652-1654.
[58]Blomhof S, spetalen S, Jacobsen MB, et al. Irritable bowel syndrome-amultifaelorial diseaes in children and adults. TiddsskrNOrlaegeforen,2002,122 (12):1213-1217.
[59]Carruthers HR, Miller V, Morris J, et al. Using art to help understand the imagery of irritable bowel syndrome and its response to hypnotherapy. Int J Clin Exp Hypn,2009,57(2):162-173.
[60]朱雪萍、陈卫昌、朱晓黎,等.脑肠肽、脑肠轴在肠易激综合征模型中作用机制研究.临床儿科杂志.2008,3(26)：236-239.
[61]Ringel Y. Brain in research infunctional gastrointestinal disorders[J]. J Clin Gastroenterol,2002,35(1Supp1):23.
[62]N Talley, P Boyce, and M Jones. Is the association between irritable bowel syndrome and abuse explained by neuroticism? A population based study. Gut,1998,42(1):47-53.
[63]董文珠,邹多武,李兆申,等.肠易激综合征患者内脏高敏性的机制研究.中华消化杂志.2004,24：18-22.
[64]Rao SS, Hatfield RA, Suls JM, et al. Psychological and physical stress induce differential effects on human colonic motility. Am J Gastroenterol,1998,93:985.
[65]Okano S, Nagaya H, Ikeura Y, et al. Effects of TAK-637, a novel neurokinin-l receptor antagonist,on colonic function in vivo. J Pharmacol Exp Ther,2001,298:559.
[66]Martinez V, Wang L Rivier J E, et al. Differential actions of peripheral corticotrophin-releasing factor (CRH), urocortin II, and urocortin III on gastric emptying and colonic transit in mice:role of CRH receptor subtypes 1 and 2. J Pharmacol Exp Ther, 2002,301:611.
[67]Saito K, Kasai T, Nagura Y, Ito H, Kanazawa M, Fukudo S. Corticotropin-releasing hormone receptor-1 antagonist blocksbraoin-gut activation induced by colonic distention in rats. Gastroenterology,2005,129 1533-43.
[68]Heinrichs, SC, TachY. TherapeuticpotentialofCRHreceptorantagonists:a gut-brain per spective. Expertopin Investig Drugs,2001,10(4):647-659.
[69]Vizzard MA, Brisson M. & De Groal WC. Transneuronal labeling Of neurons in the adult rat central nervous system following inoculation of pseudorabies virus into the colon. Cell Tissue Res,2000,299:9.
[70]李龙钦、祝金泉.促肾上腺皮质激素释放激素与结肠功能.江西医药,2005,6(40)：368-370.
[71]Jones J, Boorman J, Cann P, et al. British society of gastroenterology guidelines for the Management of theirritableb owelsy ndorme. Gut,2000,47(Suppl14,1114-1119).
[72]Fukudo S, Nomura T, Hongo M. Impact of corticotropinreleasinghormone on gastrointestinal motility and adrenocorticotropichormone in normal controls and patients with irritablebowel syndrome. Gut,1998,428:45-49.
[73]Sagami Y, Shimada Y, Tayama J, Nomura T, Satake M, Endo Y, et al. Effect of a corticotropin releasing hormone receptor antagoniston colonic sensory and motor function in patients with irritablebowel syndrome. Gut,2004,53:958-64.
[74]Saito K, Kasai T, Nagura Y, Ito H, Kanazawa M, Fukudo S. Corticotropin-releasing hormone receptor-1 antagonist blocksbraoin-gut activation induced by colonic distention in rats. Gastroenterology2005; 129 1533-43.
[75]T. Sonoda, Y. Kitamura, Y. Haku, H et al. Mast-cell precursors in various haema top oietic colonies of mice produced in vivo and in vitro[J].Br J Haematol,1983,53 (4):611-620
[76]Bischoff, G. Sellge. Mast cell hyperplasia:Role of cytokines[J]. Int Arch Allergy Immunol,2002,127 (2):118-122.
[77]Barbara G, Stanghellini V, De GiorgioR, etal. Functional gastrointe stinaldisorders and mast cells:implications for therapy[J]. Neurogastroenterol Motil,2006,18:6-17
[78]R. B. Hiatt and L. Katz. Mast cells in inflammatory conditions of the gastrointestinal tract[J]. Am J Gastroenterol,1962;37:541-545
[79]G. Barbara, R. De Giorgio, V. Stanghellini, et al. New pathophysiological mechanisms in irritable bowel syndrome[J]. Aliment Pharmacol Ther,2004,20 (Suppl 2):1-9.
[80]G. Barbara, V. Stanghellini, R. De Giorgio, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome[J]. Gastroenterology,2004,126 (3):693-702.
[81]李兆申,董文殊,邹多武,等.肠易激综合征肠粘膜肥大细胞的实验研究[J].解放军医学杂志,2002,27(7)：628-631
[82]Mar Guilarte, Javier Santos, Ine's de Tomes. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum[J]. Gut 2007,56:203-209
[83]Addolorato G, M arsigli L, Capristo E et al. Anxiety an d depression:acorllrllon feature of health care seeking patients with rritable bowel syndrome an d food allergy[J]. Hepatogastroenterology,1998,45 (23):1559-1560
[84]H. Serna, M. Porras and P. Vergara. Mast cell stabilizer ketotifen prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat[J].J Pharmacol Exp Ther,2006,319 (3):1104-1111.
[85]lovino P, Azpim F, Dimingo E, et al. The sympathetic nervous system modulates perception and reflex reponaes to gut distensilnin human [J]. Gastroenterology,1995,1-8
[86]Coelho AM, Fiarnonti J, Buem L. Systenic lipolysacacchaide influences rectal sensitivity in rats:role of mast cells, cytokines, and vagus nerve[J]. Am J physiol, 2000,279:67-81.
[87]Hebden JM, Erah DO, Blackshaw PE, et al. Increased small bowel but not colonic permeablity in post-infectious irritable bowel syndmme [J]Gastroenterology,1998; 114 (suppl):A429
[88]Oliver MR, Tan DTM, kirk DR. et al. Colonic and jejunal motor diaturbancea after colonic antigen challenge of sensitized rat[J]. Gastroeaaterology,1997,112 (6):1996.
[89]Codho, AM. Fiormnonti J, Bueno L. Mast cell degranuiafion induce delayed riced aliodynla in rats:role of histamine and 5-HT LJ].Dig Dis Sd,1998,43 (4):727-728
[90王伟岸.肠道炎症后的IBS[J].国外医学内科分册,1996,26(3)：93-96,110
[91]Gui X-Y. Mast cells:A possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the irritable bowel syndrome[J]. J Gastro enterology and Hepatology,1998,13:980-982
[92]Barbara G, Vallauce BA, Collies SM. Persistent intestinal ueuroe muscular dvsfuuctiou after acute nematode infection in mice. Gastroeuterology,1997,113: 12242-12321.
[93]Collious SM, Mcllugh K,, Jacohsou K, et al. l'rerious iuflam matiou alters the response of the rat colon to stress. Gastroeu-terology,1996,111:15119-1515.
[94]AL-Chear L, D, Kawasak M.1'asricha J, et al. A new model ofchronic visceral hypersensitivity in adult rats induced by colon irritation during pastuatal development. Gastroeuterology,2011-11:12762-12851.
[95]Williams CL, Villar Cli, letersou, JM. et al. Stress induced changes in intestinal transit in the rats:a model for irritable bowel syndrome. Gastroeuterology,1988, 94:611-621.
[96]Cue M. Uel liio-Lacheze C, L;utameue 11. et al. Stressiuducedvisceral hypersensitivity to rectal distension in rats:role of CRH and mast cells. euro Gastroeuterol Motil,1997, 9:271-279.
[97]穆振斌.黄裕新.心理性应激与胃肠动力关系的研究现状与进展.中国综合临床.2005,5：473-474.
[98]Tache Y, rrick, liavhouid Central nervous system actiou of peptides to influence gastrointestinal motor function. Gastroeuterology,19911,98:517-518.
[99]彭丽华,孙刚,杨石生.便秘型肠易激综合征新概念模型的建立.队界华人消化杂志.211114.12：112-116.
[100]刘清华,李定国.肠易激综合征动物模型复制思路和方法.国外医学：消化系疾病分册.211112,411：154-156.
[101]刘俊康,窦君,袁泽涛,等.肠道细菌潜生体诱L因素及其生物学特性与肠易激综合征相关性的研究.胃肠病学.211113.8：12.
[102]章荣华,田园华,刘俊康,等.肠道细菌潜生体形成的诱L因素实验分析.实用诊断与治疗杂志.211116.211：391-393.
[103]LevyKL, Jones KK, Wlut eheadWL, et al. lrrltahle bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroeuteroh 211111,121:799-81) t
[104]KimJ, amilleri M. Carlsou J, et al. Association of distinct adreuoceptor and serotouiu transporter polymorphisms with constipation and somatic symptoms in functional gastroiutestiual disorders. Gut,21,53:829-837.
[105]Nalihoff 131, hang L, Muuakata, J, et al. Towards au iutegrative model of irritable bowel syndrome. rogBraiu Kes,2000,122:413-423.
[106]刘雁冰,袁耀宗,陶然君,等.大鼠肠道致敏模型的建立及其内脏敏感性的评估[J].胃肠病学,2003,8(增)：7.
[107]任天华,胡品津,胡志远,等.新生期母婴分离对大鼠成年后结直肠扩张后5一羟色胺表达的影响[J].中山大学学报(医学科学版),2004,25(3)：234.
[108]李延青,杨军.肠易激综合征内脏感觉过敏动物模型的建立[J].胃肠病学和肝病学杂志,2003,12(4)：332.
[109]郭玉婷,李延青,杨军,等.肠易激综合征内脏过敏大鼠脊髓诱发电位的研究[J].胃肠病学,2004,9(6)：347.
[110]梁列新.内脏感觉功能障碍与肠易激综合征[J].中国实用内科杂志,2004,24(8)：115.
[111]Mayer E A, Collins S M. Evolving pathophysiologic models of functional gastrointestinal disorders [J]. Gastroenterology,2002,122(7):2032.
[112]Coutinho S V, Plotsky P M, Sablab M, et al. Neonatal matemal separation alters stress induced responses to viscerosomatic nociceptive stimuli in rat[J]. Am J Physiol Gastrointest Liver Physiol,2002,282(2):G307.
[113]Swatek J, Chibowski D. Endocrine cells in colorectal carcinomas, Immunohistochemical study [J]. Pol J Pathol,2000,51(3):127)
[114]Amy Foxx-Orenstein, DO, Facg, et al. IBS-Review and What's New. Med Gen Med.2006, 8(3):20.
[115Leung WK, Wu JC, Liang SM, et al. Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine:a randomized placebo-controlled trial. Am J Gastroenterol.2006,101 (7):1574-1580.
[116]Lembo AJ, Zaman M, Krueger RF et al. Psychiatric Disorder, Irritable Bowel Syndrome and Extra-Intestinal Symptoms in a Population-Based Sample of Twins. Am J Gastroenterol,2009 Feb 17 Epub ahead of print].
[117]TOC Kilkens, A Honig, MA. van Nieuwenhoven, et al. Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls. Gut,2004,53(12): 1794-1800.
[118]Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats:implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry,2009,65(3):263-267.
[2]Garnett WR. Clinical consult:management of irritable bowel syndrome [online]. J Am Soc Consultant Pharm,1999,14 (Suppl 8).
[3]Frauke Musial, Winfried Hauser, Jost Langhorst. Psychophysiology of visceral pain in IBS and health. Journal of Psychosomatic Research,2008,64:589-597.
[4]Garakani, Amir, Win, et al. Comorbidity of irritable bowel syndrome in psychiatric patients:A Review[J]. American Journal of Therapeutics,2003,10(1):61
[5]崔桂淑.肠易激综合征发病机制的研究现状及进展[J].中国煤炭工业医学杂志,2002,5(9)：865
[6]邹多武,董文珠,李兆申,等.肠易激综合征患者内脏高敏感性与肥大细胞的关系[J].第一军医大学学报,2003,24：143
[7]项柏康.重视肠易激综合征发病机理的研究及中医药治疗[J].浙江中医学院学报,2000,24：15.
[8]Small PK, London MA, Han CM, et al.Large scale ambulatory study of post prandial jejunal motility in irritable bowel syndrome[J]. Scand J Gastroenterol,1997,32:39
[9]King TS, Elia M, Hunter J. Evidence for abnormal fermentation in the irritable bowel syndrome[J]. Lancet,1998,352:1187
[10]Distefano M, Strochi A, Malservise S, et al. Non-absorbable antibiotics for managing intestinal gas production and gas related symptoms[J]. Alimentpharmacol Ther,2000, 14:1001
[11]李定国,李兆东.肠易激综合征研究现状与展望[J].中华消化杂志,2001,21(2) 69
[12]Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factor s for development of t he irritable bowel syndrome:postal survey of patients[J]. BMJ,1997,314:779-782. [13]Dobronte Z, Lakner L, Sarang K. Postinfectious irritable bowel syndrome[J]. Orv Hetil,2006,147:2077-2080.
[14]Ji S, Park H, Lee D, et al. Postinfectious irritable bowel syndrome in patients with Shigella infection[J]. J Gastroenterol Hepatol,2005,20:381-386.
[15]Barbara G, Vallance BA, Collins SM. Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice[J].Gast roenterology,1997,113:1224-1232.
[16]Gerards C, Leodolter A, Glasbrenner B, et al. H. Pylori infection and visceral hypersensitivity in patients wit h irritable bowel syndrome[J]. Dig Dis,2001,19: 170-173.
[17]Vergnolle N, Renaux B, Hollenberg MD, et al. Role of rat mast cell protease-2 in intestinal transport and barriar function. Gastroenterology,1998,114 (suppl):A674.
[18]Hebden JM, Erah PO,Blackshaw PE, et al. Increased small bowel but not colonic permeability in pos-infectious irritable bowel syndrome[J]. Gastroenterology, 1998,114(suppl):A429.
[19]范红,万萍,何旭,等.胆囊及奥狄氏括约肌功能紊乱与IBS的相关性研究[J].中国肛肠病杂志,2000,20(7)：11
[20]贾勇,王巧民,戴海明,等.肠易激综合征T淋巴细胞亚群变化及其意义[J].临床消化杂志,2002,14(2)：60-61
[21]张茹,张秀华,孙孟类,等.肠易激综合征血清中工L-8和TNF-a的变化及意义[J].中华腹部疾病杂志,2004,4(1)：7-10
[22]Stead RH. Innervation of mucosal immune cells in the gastrointestinal tract[J]. Reg Immunol,1992,4 (2):91-99
[23]Oliver MR, Tan DT, Scott RB et al, Colonic motor response to IGE-mediated mast cell degranul. ation in the Hooded-Lister rat[J]. Neurogastroenterol Motil,1996,8 (2):121-130
[24]Wood JD. Khin J.Neurotransmission at the interface of sympathetic and enteric divisions of the autonomic nervous system[J]. physiol,1999;42 (4):201-210
[25]邹多武,董文珠,李兆申,等.肠易激综合征患者内脏高敏感性与肥大细胞的关系[J].第一军医大学学报,2003,24(2)：143-146
[26]李青,王梅艳,吕国苹,等.腹部冷刺激对肠易激综合征患者内脏感觉闭值的影响[J]..胃肠病学和肝病学杂志,2002,11(4)：339-341
[27]Hasler A,Koursarakos P, Patsopoulos of irritable bowel syndromeinpatients with.increased prevalence bronchial asthma[J]. RespirMed.2003,97(1):75-79
[28]张正利,蔡淦.肠易激综合征中医论治溯源.中国中医基础医学杂志,2001,7(7)：48-50
[29]谢建群,李国霞,陆雄等.疏肝健脾汤对肠易激综合征血浆胃动素的调节作用.上海中医药杂志,2001,35(6)：13-14
[30]Zhaoxiang Bian, Ph. D, Taixtang WU, M. D, Liang Liu, Ph. D. et al. Effectiveness of the Chinese Herbal Formula TongXieYaoFang for Irritable Bowel Syndrome:A Systematic Review. THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE.2006,12(4):401-407
[31]周福生,吴文江,张庆宏.胃肠功能性疾病证型分布的统计分析.中华国际医学杂志,2002,2(5)：438-442
[32]张庆宏,周福生.析“心胃相关”.云南中医学院学报,2001,24(2)：38
[33]周福生,程宏辉,祝淑贞.心胃相关理论及临床应用,浙江中医学院学报,2004,28(2)：7-8
[35]黄适,林寿宁,雷立民,等.安肠汤结肠水疗对腹泻型肠易激综合征患者IL-1 B h和IL-10 的影响.现代中西医结合杂志.2010,19(1)：11-12.
[36]尹丽菊.二术汤加味治疗腹泻型肠易激综合症50例.吉林中医药.2002,3(22)：16.
[37]申亚东,张峰.加味逍遥散治疗腹泻型肠易激综合征85例.河南中医药学刊.2000,6(15)：37-38.
[38]邓革强,唐清珠.柔肝抑肠汤治疗腹泻型肠易激综合症37例.中医研究.2006,11(19)：30-31.
[39]温庆华,袁泉英.加味半夏泻心汤治疗肠易激综合征86例.江西中医药.2009,8(40)：33.
[40]岳妍,王文仲,杨强,等.蒺藜汤治疗腹泻型肠易激综合征.中国中医药信息杂志.2004,5(11)：447.
[41]陈玲.疏肝理肠汤治疗肠易激综合症48例.湖南中医杂志.2004,2(20)：39.
[42]黄小雄等.痛泻要方合乌梅丸治疗肠易激综合征30例体会.现代中医药.2004,5：13-14.
[43]杨军.小建中汤加减治疗肠易激综合征36例.陕西中医.2005,9(26)：920.
[44]周福生,吴文江,黄志新.顺激合剂治疗肠易激综合征综合疗效观察.广州中医药大学学报.2002,4(19)：269-271.
[45]刘炳炎.自拟久泻散治疗肠易激综合征116例.中华现代中西医杂志.2005,3(3)：248-249.
[46]王刚,李延谦,王蕾等.痛泻宁颗粒治疗腹泻型肠易激综合征(肝气乘脾证)的随机双盲安慰剂对照试验.中国询证医学杂志.2006,2(6)：84-89.
[47]王兴纬,卞晓云.王氏保赤丸联合心理治疗肠易激综合征.江苏医药.2007,8(33)：856-857.
[48]云雅卿,王红霞.加味二至丸治疗便秘型肠易激综合征验案举隅.中医临床研究.2010,10(2)：29.
[49]孙洁.健脾调肝汤治疗肠易激综合征50例.陕西中医.2005,9(26)：918-919.
[50]黄惠凤,季顺祥.固肠止泻丸联合思密达治疗腹泻型肠易激综合征疗效观察.使用中西医结合临床.2006,6(6)：11-12.
[51]左新红.中西医结合治疗腹泻型肠易激综合症32例.中医研究.2007,11(20)：34-35.
[52]赵文召,高春芳.小建中汤联合保健乳治疗肠易激综合征的临床观察.临床军医杂志.2010,3(38)：406-409.
[53]张国忠,郭丽芳,刘彦岭,等.按摩治疗便秘型肠易激综合征疗效观察.现代中西医结合杂志.2010,19(13)：1584-1585.
[54]刘慧荣,华雪桂,杨允,等.腹泻型IBS结肠黏膜5-HT表达及隔药灸治疗的临床研究.辽宁中医杂志.2006,8(33)：984-985.
[55]郭光丽,鲍虎豹,张亚滨.温针灸治疗腹泻型肠易激综合征疗效观察.现代中西医结合杂志.2010,19(16)：1998-1999.
[56]梁谊深,张越,冯金娟.太极拳运动结合穴位埋线治疗便秘型肠易激综合征疗效观察.湖北中医杂志.2010,10(32)：50-51.
[57]张志杰,张越,谢胜,等.药穴指针疗法治疗腹泻型肠易激综合征35例.陕西中医.2010,12(31)：1652-1654.
[58]Blomhof S, spetalen S, Jacobsen MB, et al. Irritable bowel syndrome-amultifaelorial diseaes in children and adults. TiddsskrNOrlaegeforen,2002,122 (12):1213-1217.
[59]Carruthers HR, Miller V, Morris J, et al. Using art to help understand the imagery of irritable bowel syndrome and its response to hypnotherapy. Int J Clin Exp Hypn,2009,57(2):162-173.
[60]朱雪萍、陈卫昌、朱晓黎,等.脑肠肽、脑肠轴在肠易激综合征模型中作用机制研究.临床儿科杂志.2008,3(26)：236-239.
[61]Ringel Y. Brain in research infunctional gastrointestinal disorders[J]. J Clin Gastroenterol,2002,35(1Supp1):23.
[62]N Talley, P Boyce, and M Jones. Is the association between irritable bowel syndrome and abuse explained by neuroticism? A population based study. Gut,1998,42(1):47-53.
[63]董文珠,邹多武,李兆申,等.肠易激综合征患者内脏高敏性的机制研究.中华消化杂志.2004,24：18-22.
[64]Rao SS, Hatfield RA, Suls JM, et al. Psychological and physical stress induce differential effects on human colonic motility. Am J Gastroenterol,1998,93:985.
[65]Okano S, Nagaya H, Ikeura Y, et al. Effects of TAK-637, a novel neurokinin-l receptor antagonist,on colonic function in vivo. J Pharmacol Exp Ther,2001,298:559.
[66]Martinez V, Wang L Rivier J E, et al. Differential actions of peripheral corticotrophin-releasing factor (CRH), urocortin II, and urocortin III on gastric emptying and colonic transit in mice:role of CRH receptor subtypes 1 and 2. J Pharmacol Exp Ther, 2002,301:611.
[67]Saito K, Kasai T, Nagura Y, Ito H, Kanazawa M, Fukudo S. Corticotropin-releasing hormone receptor-1 antagonist blocksbraoin-gut activation induced by colonic distention in rats. Gastroenterology,2005,129 1533-43.
[68]Heinrichs, SC, TachY. TherapeuticpotentialofCRHreceptorantagonists:a gut-brain per spective. Expertopin Investig Drugs,2001,10(4):647-659.
[69]Vizzard MA, Brisson M. & De Groal WC. Transneuronal labeling Of neurons in the adult rat central nervous system following inoculation of pseudorabies virus into the colon. Cell Tissue Res,2000,299:9.
[70]李龙钦、祝金泉.促肾上腺皮质激素释放激素与结肠功能.江西医药,2005,6(40)：368-370.
[71]Jones J, Boorman J, Cann P, et al. British society of gastroenterology guidelines for the Management of theirritableb owelsy ndorme. Gut,2000,47(Suppl14,1114-1119).
[72]Fukudo S, Nomura T, Hongo M. Impact of corticotropinreleasinghormone on gastrointestinal motility and adrenocorticotropichormone in normal controls and patients with irritablebowel syndrome. Gut,1998,428:45-49.
[73]Sagami Y, Shimada Y, Tayama J, Nomura T, Satake M, Endo Y, et al. Effect of a corticotropin releasing hormone receptor antagoniston colonic sensory and motor function in patients with irritablebowel syndrome. Gut,2004,53:958-64.
[74]Saito K, Kasai T, Nagura Y, Ito H, Kanazawa M, Fukudo S. Corticotropin-releasing hormone receptor-1 antagonist blocksbraoin-gut activation induced by colonic distention in rats. Gastroenterology2005; 129 1533-43.
[75]T. Sonoda, Y. Kitamura, Y. Haku, H et al. Mast-cell precursors in various haema top oietic colonies of mice produced in vivo and in vitro[J].Br J Haematol,1983,53 (4):611-620
[76]Bischoff, G. Sellge. Mast cell hyperplasia:Role of cytokines[J]. Int Arch Allergy Immunol,2002,127 (2):118-122.
[77]Barbara G, Stanghellini V, De GiorgioR, etal. Functional gastrointe stinaldisorders and mast cells:implications for therapy[J]. Neurogastroenterol Motil,2006,18:6-17
[78]R. B. Hiatt and L. Katz. Mast cells in inflammatory conditions of the gastrointestinal tract[J]. Am J Gastroenterol,1962;37:541-545
[79]G. Barbara, R. De Giorgio, V. Stanghellini, et al. New pathophysiological mechanisms in irritable bowel syndrome[J]. Aliment Pharmacol Ther,2004,20 (Suppl 2):1-9.
[80]G. Barbara, V. Stanghellini, R. De Giorgio, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome[J]. Gastroenterology,2004,126 (3):693-702.
[81]李兆申,董文殊,邹多武,等.肠易激综合征肠粘膜肥大细胞的实验研究[J].解放军医学杂志,2002,27(7)：628-631
[82]Mar Guilarte, Javier Santos, Ine's de Tomes. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum[J]. Gut 2007,56:203-209
[83]Addolorato G, M arsigli L, Capristo E et al. Anxiety an d depression:acorllrllon feature of health care seeking patients with rritable bowel syndrome an d food allergy[J]. Hepatogastroenterology,1998,45 (23):1559-1560
[84]H. Serna, M. Porras and P. Vergara. Mast cell stabilizer ketotifen prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat[J].J Pharmacol Exp Ther,2006,319 (3):1104-1111.
[85]lovino P, Azpim F, Dimingo E, et al. The sympathetic nervous system modulates perception and reflex reponaes to gut distensilnin human [J]. Gastroenterology,1995,1-8
[86]Coelho AM, Fiarnonti J, Buem L. Systenic lipolysacacchaide influences rectal sensitivity in rats:role of mast cells, cytokines, and vagus nerve[J]. Am J physiol, 2000,279:67-81.
[87]Hebden JM, Erah DO, Blackshaw PE, et al. Increased small bowel but not colonic permeablity in post-infectious irritable bowel syndmme [J]Gastroenterology,1998; 114 (suppl):A429
[88]Oliver MR, Tan DTM, kirk DR. et al. Colonic and jejunal motor diaturbancea after colonic antigen challenge of sensitized rat[J]. Gastroeaaterology,1997,112 (6):1996.
[89]Codho, AM. Fiormnonti J, Bueno L. Mast cell degranuiafion induce delayed riced aliodynla in rats:role of histamine and 5-HT LJ].Dig Dis Sd,1998,43 (4):727-728
[90王伟岸.肠道炎症后的IBS[J].国外医学内科分册,1996,26(3)：93-96,110
[91]Gui X-Y. Mast cells:A possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the irritable bowel syndrome[J]. J Gastro enterology and Hepatology,1998,13:980-982
[92]Barbara G, Vallauce BA, Collies SM. Persistent intestinal ueuroe muscular dvsfuuctiou after acute nematode infection in mice. Gastroeuterology,1997,113: 12242-12321.
[93]Collious SM, Mcllugh K,, Jacohsou K, et al. l'rerious iuflam matiou alters the response of the rat colon to stress. Gastroeu-terology,1996,111:15119-1515.
[94]AL-Chear L, D, Kawasak M.1'asricha J, et al. A new model ofchronic visceral hypersensitivity in adult rats induced by colon irritation during pastuatal development. Gastroeuterology,2011-11:12762-12851.
[95]Williams CL, Villar Cli, letersou, JM. et al. Stress induced changes in intestinal transit in the rats:a model for irritable bowel syndrome. Gastroeuterology,1988, 94:611-621.
[96]Cue M. Uel liio-Lacheze C, L;utameue 11. et al. Stressiuducedvisceral hypersensitivity to rectal distension in rats:role of CRH and mast cells. euro Gastroeuterol Motil,1997, 9:271-279.
[97]穆振斌.黄裕新.心理性应激与胃肠动力关系的研究现状与进展.中国综合临床.2005,5：473-474.
[98]Tache Y, rrick, liavhouid Central nervous system actiou of peptides to influence gastrointestinal motor function. Gastroeuterology,19911,98:517-518.
[99]彭丽华,孙刚,杨石生.便秘型肠易激综合征新概念模型的建立.队界华人消化杂志.211114.12：112-116.
[100]刘清华,李定国.肠易激综合征动物模型复制思路和方法.国外医学：消化系疾病分册.211112,411：154-156.
[101]刘俊康,窦君,袁泽涛,等.肠道细菌潜生体诱L因素及其生物学特性与肠易激综合征相关性的研究.胃肠病学.211113.8：12.
[102]章荣华,田园华,刘俊康,等.肠道细菌潜生体形成的诱L因素实验分析.实用诊断与治疗杂志.211116.211：391-393.
[103]LevyKL, Jones KK, Wlut eheadWL, et al. lrrltahle bowel syndrome in twins:heredity and social learning both contribute to etiology. Gastroeuteroh 211111,121:799-81) t
[104]KimJ, amilleri M. Carlsou J, et al. Association of distinct adreuoceptor and serotouiu transporter polymorphisms with constipation and somatic symptoms in functional gastroiutestiual disorders. Gut,21,53:829-837.
[105]Nalihoff 131, hang L, Muuakata, J, et al. Towards au iutegrative model of irritable bowel syndrome. rogBraiu Kes,2000,122:413-423.
[106]刘雁冰,袁耀宗,陶然君,等.大鼠肠道致敏模型的建立及其内脏敏感性的评估[J].胃肠病学,2003,8(增)：7.
[107]任天华,胡品津,胡志远,等.新生期母婴分离对大鼠成年后结直肠扩张后5一羟色胺表达的影响[J].中山大学学报(医学科学版),2004,25(3)：234.
[108]李延青,杨军.肠易激综合征内脏感觉过敏动物模型的建立[J].胃肠病学和肝病学杂志,2003,12(4)：332.
[109]郭玉婷,李延青,杨军,等.肠易激综合征内脏过敏大鼠脊髓诱发电位的研究[J].胃肠病学,2004,9(6)：347.
[110]梁列新.内脏感觉功能障碍与肠易激综合征[J].中国实用内科杂志,2004,24(8)：115.
[111]Mayer E A, Collins S M. Evolving pathophysiologic models of functional gastrointestinal disorders [J]. Gastroenterology,2002,122(7):2032.
[112]Coutinho S V, Plotsky P M, Sablab M, et al. Neonatal matemal separation alters stress induced responses to viscerosomatic nociceptive stimuli in rat[J]. Am J Physiol Gastrointest Liver Physiol,2002,282(2):G307.
[113]Swatek J, Chibowski D. Endocrine cells in colorectal carcinomas, Immunohistochemical study [J]. Pol J Pathol,2000,51(3):127)
[114]Amy Foxx-Orenstein, DO, Facg, et al. IBS-Review and What's New. Med Gen Med.2006, 8(3):20.
[115Leung WK, Wu JC, Liang SM, et al. Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine:a randomized placebo-controlled trial. Am J Gastroenterol.2006,101 (7):1574-1580.
[116]Lembo AJ, Zaman M, Krueger RF et al. Psychiatric Disorder, Irritable Bowel Syndrome and Extra-Intestinal Symptoms in a Population-Based Sample of Twins. Am J Gastroenterol,2009 Feb 17 Epub ahead of print].
[117]TOC Kilkens, A Honig, MA. van Nieuwenhoven, et al. Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls. Gut,2004,53(12): 1794-1800.
[118]Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats:implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry,2009,65(3):263-267.