CRH在脑梗塞相关胃肠屏障破坏中的作用
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摘要
目的:研究CRH在脑梗塞相关胃肠屏障破坏中的作用及其途径。
方法:雄性Wistar大鼠60只,随机分为空白组(B组)、伪手术组(C组)、脑梗塞组(Ⅰ组)、脑梗塞+脑室α-螺旋-CRH(9-41)组(Aic组)、脑梗塞+腹腔CRH组(H组)、脑梗塞+腹腔α-螺旋-CRH(9-41)组(Aip组),每组10只。留尿检测尿肾上腺素、去甲肾上腺素、皮质醇含量及蔗糖排出率,造模后24小时行血浆二胺氧化酶(DAO)活性、血浆D-乳酸(D-lac)浓度、血浆内毒素(LPS)浓度检测;行胃大体Guth评分,光镜下对胃肠粘膜病理形态进行观察;WesternBlot法检测下丘脑、胃、空肠、结肠CRH蛋白的表达;免疫组化法进行胃肠CRH蛋白定位,Realtime-PCR法检测下丘脑、胃、空肠、结肠CRHmRNA的表达。
结果:Ⅰ组、Aic组、H组和Aip组的大鼠行为学证实均出现脑梗塞。各组应激强度指标24小时尿肾上腺素、去甲肾上腺素、皮质醇含量变化趋势一致:Ⅰ组≈H组≈Aip组>Aic组≈C组≈B组。各组尿蔗糖排出率、胃大体、光镜下评分和下丘脑CRH含量、CRHmRNA含量变化趋势一致:Ⅰ组≈Aip组>Aic组≈H组≥C组≈B组。各组血浆LPS、D-乳酸、二胺氧化酶活性和空肠、结肠CRH含量、CRHmRNA含量变化趋势一致:Ⅰ组>Aip组≥Aic组≈H组≥C组≈B组。24小时尿肾上腺素、去甲肾上腺素、皮质醇含量、尿蔗糖排出率、胃大体评分和下丘脑CRH含量正相关。血浆LPS、D-乳酸、二胺氧化酶活性和空肠CRH含量正相关。
结论:(1)脑梗塞时,HPA轴和SNS激活,下丘脑和胃肠组织的CRH蛋白含量升高,胃肠道的通透性增加,粘膜屏障破坏。(2)脑梗塞相关的胃肠屏障破坏与皮质醇及儿茶酚胺存在因果关系的可能性极小。(3)CRH是脑梗塞相关胃肠屏障破坏的重要因素。可以通过对CRH的干涉调控应激,减轻急性疾病患者的应激性胃肠屏障损伤。(4)中枢使用CRH受体拮抗剂能缓解脑梗塞相关的胃肠屏障破坏。(5)外周使用CRH受体拮抗剂能缓解脑梗塞相关的肠屏障破坏而不能缓解脑梗塞相关的胃屏障破坏。(6)脑梗塞后外周给予CRH会抑制脑内和胃肠道局部的CRH蛋白的转录和表达。(7)脑梗塞相关的胃屏障破坏和下丘脑及胃组织的CRH蛋白含量都正相关;脑梗塞相关的肠屏障破坏和肠道局部组织的CRH蛋白含量正相关而和下丘脑的CRH蛋白含量不相关。
Objective:To investigate the role of CRH in the gastrolintestinal barrier changes in cerebral infarction and explore it's possible underneath mechanism.
Methods:60 male Wistar rats were randomly divided into 6 groups with 10 each:Blank group(group B),sham operation group(group C),infarction group(group I),infarction+α-h-CRH(9-41) ic group(group Aic),infarction+α-h-CRH(9-41) ip group(group Aip),infarction+CRH ip group(group H).Blood samples were taken 24h after operation.The plasma activity of diamine oxidase(DAO) concentration of plasma D-lactate and plasma Lipopolysaccharide(LPS) were measured.24h urine were collected to detect urinary cortisol, urinary catecholamines(norepinephrine and epinephrine) and sucrose excretion.Gastric gross ulcer score and histological score of the gastrolintestinal were also determined. Immunohistochemistry was used to analysis the changes of CRH protein localizing in the gastrointestinal tract.WesternBlot and Realtime-PCR technology were used to detect the CRH protein and CRHmRNA in the hypothalamus and gastrointestinal tract.
Results:Cerebral infarction was confirmed by NSS in all groups of rat in group I,group Aic, group H and group Aip.The results of the tendency of 24h urinary cortisol,urinary norepinephrine,urinary epinephrine were concurrent:group I≈group H≈group Aip＞group Aicgroup C≈group B。The results of the tendency of sucrose excretion,gastric gross ulcer score,gastric histological score and hypothalamus CRH protein/mRNA were concurrent: group I≈group Aip＞group Aicgroup H≥group C≈group B.The results of the tendency of plasma activity of DAO,plasma D-lactate,plasma LPS,the gut histological score and gut CRH protein/mRNA content were concurrent:group I＞group Aip≥group Aic≈group H≥group C≈group B.There were positive correlations between sucrose excretion,gastric gross ulcer score,24h urinary cortisol,urinary norepinephrine,urinary epinephrine and hypothalamus CRH protein;between the level of plasma D-lac,plasma activity of DAO, plasma LPS and gut CRH protein.
Conclusions:(l)The gastrointestinal tract barrier dysfunction will show up with the activation of HPA axis,SNS and the elvation of CRH protein in the hypothalamus and gastrointestinal tract after cerebral infarction.(2) The infarction related gastrointestinal barrier dysfunction is occure probably not because of cortisol or catecholamine.(3)CRH is closely related to the infarction related gastrointestinal barrier dysfunction.We may suppress this kind of stress related gastrointestinal barrier dysfunction through interfere the activity of CRH in the hypothalamus or the gastrointestinal tissue.(4) Central use of CRH antagonistα-h-CRH(9-41) will suppress the infarction related gastrointestinal barrier dysfunction to a certain degree.(5)Peripheral use of CRH antagonist a-h-CRH(9-41) will suppress the infarction related intestinal but not gastric barrier dysfunction to a certain degree(6) Peripheral use of CRH can suppress the concentration of CRH protein/CRHmRNA in the gastrointestinal tract and hypothalamus.(7)Infarction related gastric barrier dysfunction is correlated with CRH protein in the hypothalamus and stomach,Infarction related intestinal barrier dysfunction is correlated with CRH protein in the intestinal tract but not in the hypothalamus.
方法:雄性Wistar大鼠60只,随机分为空白组(B组)、伪手术组(C组)、脑梗塞组(Ⅰ组)、脑梗塞+脑室α-螺旋-CRH(9-41)组(Aic组)、脑梗塞+腹腔CRH组(H组)、脑梗塞+腹腔α-螺旋-CRH(9-41)组(Aip组),每组10只。留尿检测尿肾上腺素、去甲肾上腺素、皮质醇含量及蔗糖排出率,造模后24小时行血浆二胺氧化酶(DAO)活性、血浆D-乳酸(D-lac)浓度、血浆内毒素(LPS)浓度检测;行胃大体Guth评分,光镜下对胃肠粘膜病理形态进行观察;WesternBlot法检测下丘脑、胃、空肠、结肠CRH蛋白的表达;免疫组化法进行胃肠CRH蛋白定位,Realtime-PCR法检测下丘脑、胃、空肠、结肠CRHmRNA的表达。
结果:Ⅰ组、Aic组、H组和Aip组的大鼠行为学证实均出现脑梗塞。各组应激强度指标24小时尿肾上腺素、去甲肾上腺素、皮质醇含量变化趋势一致:Ⅰ组≈H组≈Aip组>Aic组≈C组≈B组。各组尿蔗糖排出率、胃大体、光镜下评分和下丘脑CRH含量、CRHmRNA含量变化趋势一致:Ⅰ组≈Aip组>Aic组≈H组≥C组≈B组。各组血浆LPS、D-乳酸、二胺氧化酶活性和空肠、结肠CRH含量、CRHmRNA含量变化趋势一致:Ⅰ组>Aip组≥Aic组≈H组≥C组≈B组。24小时尿肾上腺素、去甲肾上腺素、皮质醇含量、尿蔗糖排出率、胃大体评分和下丘脑CRH含量正相关。血浆LPS、D-乳酸、二胺氧化酶活性和空肠CRH含量正相关。
结论:(1)脑梗塞时,HPA轴和SNS激活,下丘脑和胃肠组织的CRH蛋白含量升高,胃肠道的通透性增加,粘膜屏障破坏。(2)脑梗塞相关的胃肠屏障破坏与皮质醇及儿茶酚胺存在因果关系的可能性极小。(3)CRH是脑梗塞相关胃肠屏障破坏的重要因素。可以通过对CRH的干涉调控应激,减轻急性疾病患者的应激性胃肠屏障损伤。(4)中枢使用CRH受体拮抗剂能缓解脑梗塞相关的胃肠屏障破坏。(5)外周使用CRH受体拮抗剂能缓解脑梗塞相关的肠屏障破坏而不能缓解脑梗塞相关的胃屏障破坏。(6)脑梗塞后外周给予CRH会抑制脑内和胃肠道局部的CRH蛋白的转录和表达。(7)脑梗塞相关的胃屏障破坏和下丘脑及胃组织的CRH蛋白含量都正相关;脑梗塞相关的肠屏障破坏和肠道局部组织的CRH蛋白含量正相关而和下丘脑的CRH蛋白含量不相关。
Objective:To investigate the role of CRH in the gastrolintestinal barrier changes in cerebral infarction and explore it's possible underneath mechanism.
Methods:60 male Wistar rats were randomly divided into 6 groups with 10 each:Blank group(group B),sham operation group(group C),infarction group(group I),infarction+α-h-CRH(9-41) ic group(group Aic),infarction+α-h-CRH(9-41) ip group(group Aip),infarction+CRH ip group(group H).Blood samples were taken 24h after operation.The plasma activity of diamine oxidase(DAO) concentration of plasma D-lactate and plasma Lipopolysaccharide(LPS) were measured.24h urine were collected to detect urinary cortisol, urinary catecholamines(norepinephrine and epinephrine) and sucrose excretion.Gastric gross ulcer score and histological score of the gastrolintestinal were also determined. Immunohistochemistry was used to analysis the changes of CRH protein localizing in the gastrointestinal tract.WesternBlot and Realtime-PCR technology were used to detect the CRH protein and CRHmRNA in the hypothalamus and gastrointestinal tract.
Results:Cerebral infarction was confirmed by NSS in all groups of rat in group I,group Aic, group H and group Aip.The results of the tendency of 24h urinary cortisol,urinary norepinephrine,urinary epinephrine were concurrent:group I≈group H≈group Aip＞group Aicgroup C≈group B。The results of the tendency of sucrose excretion,gastric gross ulcer score,gastric histological score and hypothalamus CRH protein/mRNA were concurrent: group I≈group Aip＞group Aicgroup H≥group C≈group B.The results of the tendency of plasma activity of DAO,plasma D-lactate,plasma LPS,the gut histological score and gut CRH protein/mRNA content were concurrent:group I＞group Aip≥group Aic≈group H≥group C≈group B.There were positive correlations between sucrose excretion,gastric gross ulcer score,24h urinary cortisol,urinary norepinephrine,urinary epinephrine and hypothalamus CRH protein;between the level of plasma D-lac,plasma activity of DAO, plasma LPS and gut CRH protein.
Conclusions:(l)The gastrointestinal tract barrier dysfunction will show up with the activation of HPA axis,SNS and the elvation of CRH protein in the hypothalamus and gastrointestinal tract after cerebral infarction.(2) The infarction related gastrointestinal barrier dysfunction is occure probably not because of cortisol or catecholamine.(3)CRH is closely related to the infarction related gastrointestinal barrier dysfunction.We may suppress this kind of stress related gastrointestinal barrier dysfunction through interfere the activity of CRH in the hypothalamus or the gastrointestinal tissue.(4) Central use of CRH antagonistα-h-CRH(9-41) will suppress the infarction related gastrointestinal barrier dysfunction to a certain degree.(5)Peripheral use of CRH antagonist a-h-CRH(9-41) will suppress the infarction related intestinal but not gastric barrier dysfunction to a certain degree(6) Peripheral use of CRH can suppress the concentration of CRH protein/CRHmRNA in the gastrointestinal tract and hypothalamus.(7)Infarction related gastric barrier dysfunction is correlated with CRH protein in the hypothalamus and stomach,Infarction related intestinal barrier dysfunction is correlated with CRH protein in the intestinal tract but not in the hypothalamus.
引文
[1]Lennard DE,Eckert WA,Merchenthaler I.Corticotropin—releasing hormone neurons in the paraventricular nucleus project to the external zone of the median eminence:a study combining retrograde labeling with imrnunocytochemistry[J].J Neuroendocrinol,1993,5 (2):175-181.
[2]Spiess J,Rivier J,Rivier C,et al.Primary structure of corticotrophin-releasing factor from ovine hypothalamus[J].Proc Natl Acad SciUSA,1981,78 (10):6517-6521.
[3]Mayer EA.The neurobiology of stress and gastrointestinal disease[J].Gut 2000;47(6):861-9.
[4]Bakshi V P,Kalin N H.Corricotropin-Releasing hormone and animal models of anxiety:gene-environment Interactions[J].J .B iolPsychiatry,2000,48 (12):1175-98.
[5]Bale TL,Vale WW.CRF and CRF receptors:Role in stress responsivity and other behaviors[J].Ann Rev Pharmacol Toxicol 2004;44:525-557.
[6]Meddings JB,Sutherland LR,Byles NI.Sucrose:a novel permeability marker for gastroduodenal disease.Gastroenterology[J].Gastroenterology.1993 Jun;104(6):1619-26.
[7]Sutherl LR,Verhoef M,Wallace JL,et al.A simple,non-invasive marker of gastric damage:sucrose permeability[J].Lancet,1994;343:998-1000.
[8]Tsunooka N,Maeyama K,Hamada Y,et al.Bacterial translocation secondary to small intestinal mucosal ischemia during cardiopulmonary bypass.Measurement by diamine oxidase and peptidoglycan[J].Eur J Cardiothorac Surg.2004 Feb;25(2):275-80.
[9]Johnston SD,Smye M,Watson RP.Intestinal permeability tests in coeliac disease[J].Clin Lab.2001;47(3-4):143-50.
[10]Magnotti LJ,Deitch EA.Burns,bacterial translocation,gut barrier function,and failure[J].J Burn Care Rehabil.2005 Sep-Oct;26(5):383-91.
[11]Charmandari E,Tsigos C,Chrousos G.et al.Endocrinology of the stress response[J].Annu Rev Physiol.2005;67:259-84.
[12]Dantzer R,Mormede P.Stress in farm animals:a need forreevaluation[J].J Anim Sci.1983 Jul;57(l):6-18.
[13]Fibiger W,Singer G,Miller AJ,et al.Cortisol and catecholamines changes as functions of time-of-day and self-reported mood[J].Neurosci Biobehav Rev.1984 Winter;8(4):523-30.
[14]M.Hay,M.C.Meunier-Salaun,F.Brulaud,et al.Assessment of hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity in pregnant sows through the measurement of glucocorticoids and catecholamines in urine[J].J Anim Sci 2000.78:420-428.
[15]Koizumi J,Yoshida Y,Nakazwa F,et al.Experimental studies of ischemic brain edema:1 .A new experimental mode of cerebral embolism in rats in which recirlation can be introduced in the ischemic area[J].Stroke,1986,8:128.
[16]Davies NM,Corrigan BW,Jamali F.Sucrose urinary excretion in the rat measured using a simple assay:a model of gastroduodenal permeability[J].Pharm Res.1995 Nov;12(l l):1733-6.
[17]Morimoto A,Nakamori T,Morimoto K,Tan N,Murakami N.The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats[J].Journal of Physiology 1993;460,pp.221-229.
[18]Santos J,Saunders PR,Hanssen NP,Yang PC,Yates D,Groot JA,and Perdue MH.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in therat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[19]Javier Santos,Paul R.Saunders,Nico P.M.Hanssen,et al .Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[20]PaxinosG,WatsonC.The Rat Brain in Stereotaxie Coordinates,4th edition[J].Academie Press,New York,1998.
[21]Longa EZ,Weinstein PR.Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20 (1):84-91.
[22]Chiu CJ,McArdle AH,Brown R,et al.Intestinal mucosal lesion in low-flow states.I.A morphological,hemodynamic,and metabolic reappraisal[J].Arch Surg,1970;101:478-483.
[23]Selye H.A syndrome produced by diverse nocuous agents[J].Nature1936;138:32-36.
[24]Thomson AB,Keelan M,Thiesen A,et al.Small bowel review,normal physiology part 2[J].Dig Dis Sci.2001 Dec;46(12):2588-2607.
[25]Schilling D et al.Low seroprevalence of Helicobacter pylori infection in patients with stress ulcer bleeding-a prospective evaluation of patients on a cardiosurgical intensive care unit[J].Intensive Care Med 2000;26:1832-1836.
[26]O'Donnell MJ,Kapral MK,Fang J,et al.Gastrointestinal bleeding after acute ischemic stroke[J].Neurology.2008 Aug 26;71(9):650-5.
[27]Deitch EA.Bacterial translocation or lymphatic drainage of toxic products from the gut:what is important in human beings?[J].Surgery.2002 Mar,131(3):241-244.
[28]Spirt MJ.Stress-related mucosal disease:risk factors and prophylactic therapy[J].Clin Ther.2004 Feb:26(2):197-213.
[29]Steinberg KP.Stress-related mucosal disease in the critically ill patient:risk factors and strategies to prevent stress-related bleeding in the intensive care unit[J].Crit Care Med.2002 Jun;30(6Suppl):S362-4.
[30]Stollman N.Metz DC.Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients[J].Crit Care.2005 Mar;20(l):35-45.
[31]Bhatia V,Tandon RK.Stress and the gastrointestinal tract[J].J Gastroenterol Hepatol.2005 Mar;20(3):332-9.
[32]Caso JR,Leza JC,Menchen L.The effects of physical and psychological stress on the gastro-intestinal tract:lessons from animal models[J].Curr Mol Med.2008 Jun;8(4):299-312.
[33]Bederson JB,Pitts LH,TsujiM,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke,1986,17 (3) .472-476.
[34]Alexis NE.Dietrich WD,Green EJ,et al.Nonocclusive common carotid artery thrombosis in the rat results in reversible sensorimotor and cognitive behavioral deficits[J].Stroke,1995,26 (12):2338-2346.
[35]Liu XG,Xu LN.A rat middle cerebral artery thrombosis model for evaluation of thrombolytic and antithrombotic agents[J].ActaPharmSin,1995,30 (9):662-667.
[36]Wang W,Dong WW,Fu YG,et al.The MCA occlusion and reperfusion model induced by photochemico!ogy[J].ChinJ NeuruMent Dis,1996,22 (1):27-30.
[37]Saunders PR,Kosecka U,McKay DM,et al.Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine[J].Am J Physiol,1994;267(5Ptl);G794-799.
[38]Yoshimura H,Kan N,Ogawa N.Preventive and curative effects of prostaglandins on stress ulcer in rats[J].Dig Dis Sci 34:436-444,1989.
[39]Wallace J,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,1996 May;10(7):731-40.
[40]Levine BA.Pathophysiology and mechanisms of stress ulcer injury[J].Pharmacotherapy.1987;7(6 Pt 2):90S-94S.
[41]Yabana T,Yachi A.Stress-induced vascular damage and ulcer[J].Dig Dis Sci.1988 Jun;33(6):751-61.
[42]Konturek PC,Brzozowski T,Konturek SJ,et al.Apoptosis in gastric mucosa with stress-induced gastric ulcers[J].J Physiol Pharmacol.1999 Jun;50(2):211-25.
[43]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Pharm Sci Technol Today,1999 Jul,2(7):281-287.
[44]van der Hulst RR,von Meyenfeldt MF,van Kreel BK,et al.Gut permeability,intestinal morphology,and nutritional depletion[J].Nutrition.1998 Jan;14(l):l-6.
[45]MacFie J.Enteral versus parenteral nutrition:the significance of bacterial translocation and gut-barrier function[J].Nutrition,2000 Jul-Aug,16(7-8):606-611.
[46]Santos J,Saperas E,Mourelle M,et al.Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats[J].Gastroenterology,1996;111 (6);1465-1473.
[47]Santos J,Yang PC,So'derholm JD,Benjamin M,and PerdueMH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 48:630-636,2001.
[48]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J],Gastroenterology,2000;119(4);1019-1028.
[49]Madara JL.Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium:physiological rearrangement of tight junctions[J].J Membr Biol,1990;116(2);177-184.
[50]Kiliaan AJ,Saunders PR,Bijlsma PB et al.Stress stimulates transepithelial macromolecular uptake in rat jejunum[J].Am.J.Physiol.Gastrointest.Liver Physiol.1998;275 (5 Part 1):G1037-G1044.
[51]Wilson,LM,and Baldwin AL.Environmental stress causes mast cell degranulation,endothelial and epithelial changes,and edema in the rat intestinal mucosa[J].Microcirculation 1999,6:189-198.
[52]Spitz,JC,Ghandi S,Taveras M,Aoys E,and Alverdy JC.Characteristics of the intestinal epithelial barrier during dietary manipulation and glucocorticoid stress[J].Crit Care Med 1996,24:635-641.
[53]So'derholm JD,Yang PC,Ceponis P,et al.Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine[J].Gastroenterology.2002 Oct;123(4):1099-108.
[54]Bailey,MT,and Coe CL.Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys[J].Dev Psychobiol 1999,35:146-155.
[55]Castagliuolo I,Lamont JT,Qiu B,et al.Acute stress causes mucin release from rat colon:role of corticotropin releasing factor and mast cells[J].Am J Physiol,1996;271(5Ptl):G884-892.
[56]Coplan JD,Andrews MW,Rosenblum LA,et al.Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors:implications for the pathophysiology of mood and anxiety disorders[J].Proc Natl Acad Sci USA 1996 93:1619-1623.
[57]Bakshi VP,KalinNH.Corticotropin-releasing hormone and animal models of anxiety:gene-environment interactions[J].Biol Psychiatry 2000 48:1175-1198.
[58]Banks WA and Kastin A J.Passage of peptides across the blood-brain barrier:Pathophysiological perspectives[J].Life Sci 1996;59:1923-1943.
[59]Riviere PJ,Pascaud X,Chevalier E,Junien JL.Fedotozine reversal of peritoneal-irritation-induced ileus in rats:Possible peripheral action on sensory afferents[J].J Pharmacol Exp Ther 1994;270:846-850.
[60]Habib KE et al.Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral,neuroendocrine,and autonomic responses to stress in primates[J].Proc Natl Acad Sci U S A 2000;97:6079-6084.
[61]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,et al.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry 2002;7:474-483.
[62]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil 2004;16:137-142.
[63]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J].Gastroenterology.2000 Oct;119(4):1019-28.
[64]Dunn AJ,Berridge CW.Physiological and behavioral responses to corticotropin-releasing factor administration:is CRF a mediator of anxiety or stress responses?[J].Brain Res Rev 1990;15:71-100.
[65]Valentino RJ,Page M,Van Bockstaele E,et al .Corticotropin-releasing factor innervation of the locus coeruleus region:distribution of fibers and sources of input[J].Neuroscience.1992;48(3):689-705.
[66]Valentino RJ,Foote SL,Aston-Jones G.Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus[J].Brain Res.1983 Jul 4;270(2):363-7.
[67]Jezova D,Ochedalski T,Glickman M,et al .Central corticotrophin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress[J].J .Neuroscience,1999,94(3):797-802.
[68]Hank P.Jedemal and Anthony A.Grace.Corticotropin-Releasing Hormone Directly Activates Noradrenergic Neurons of the Locus Ceruleus Recorded In Vitro[J].J Neuroscience,2004 24(43):9703-9713.
[69]Sawchenko PE,Swanson LW.The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat[J].Brain Res.1982 Nov;257(3):275-325.
[70]Overton JM,Fisher LA.Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats[J].J Auton Nerv Syst.1991 Jul;35(l):43-51.
[71]McCann SM,Antunes RJ,Franci CR.Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection[J].J .Braz J Med Biol Res,2000,33 (10):1121-1131.
[72]Lyons MK,Anderson RE,Meyer FB.Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury[J].Brain Res.1991 Apr 5;545(l-2):339-42.
[73]Strijbos PJ,Relton JK,Rothwell NJ.Corticotrophin-releasing factor antagonist inhibits neuronal damage induced by focal cerebral ischaemia or activation of NMDA receptors in the rat brain[J].Brain Res.1994 Sep 12;656(2):405-8.
[74]Choi DI,Park SK,Kim HS,et al.Expression of corticotropin releasing factor,but not its binding protein,in CA1 pyramidal cells of gerbil hippocampus following transient ischemia[J],Brain Res.2001 Apr 27;899(l-2):255-9.
[75]Wong ML,Loddick SA,Bongiorno PB,et al.Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala[J].Neuroreport.1995 Sep 11;6(13):1785-8.
[76]Mackay KB,Bozigian H,Grigoriadis DE,et al.Neuroprotective effects of the CRFI antagonist R121920 after permanent focal ischemia in the rat[J].J Cereb Blood Flow Metab.2001 Oct;21(10):1208-]4.
[77]Habib KE,Negro PJ,Sciullo D,Dib A,Gold PW.Protective role of the sympathoadrenal system against stress-induced gastric mucosal injury in the rat[J].Gastroenterology 1999;116:G0783.
[78]Hernandez DE.Neuroendocrine mechanisms of stress ulceration:focus on thyrotropin-releasing hormone[J].Life Sci 1986;39:279-296.
[79]Grijalva CV,Novin D.The role of the hypothalamus and dorsal vagal complex in gastrointestinal function and pathophysiology[J].Ann N Y Acad Sci 1990;597:207-222.
[80]Weiner H.From simplicity to complexity (1950-1990):the case of peptic ulceration-Ⅱ.Animal studies[J].Psychosom Med 1991;53:491-516.
[81]Weichert RF,3rd,Ellison JP,Woolverton WC,Drapanas T.Postvagotomy serotonin depletion in mucosal mast cells of the rat stomach[J].Surg Forum 1970;21:318-320.
[82]Williams CL,Villar RG,Peterson JM,Burks TF.Stress-induced changes in intestinal transit in the rat:a model for irritable bowel syndrome[J].Gastroenterology 1988;94:611-621.
[83]Soderholm JD,Yates DA,Gareau MG,et al.Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress[J].Am J Physiol Gastrointest Liver Physiol.2002 Dec;283(6):G1257-63.
[84]V.Martinez! and Y.Tache.CRFI Receptors as a Therapeutic Target for Irritable Bowel Syndrome[J].Current Pharmaceutical Design,2006,12,4071-4088.
[85]Castagliuolo I,Wershil BK,Karalis K,Pasha A,Nikulasson ST,Bisschops C.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol Gastrointest Liver Physiol 1998;274:G1094-G1100.
[86]Fukudo S.Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation[J].J Gastroenterol.2007 Jan;42 Suppl 17:48-51.
[87]Ayala AR,Pushkas J,Higley JD,et al.Behavioral,Adrenal,and Sympathetic Responses to Long-Term Administration of an Oral Corticotropin-Releasing Hormone Receptor Antagonist in a Primate Stress Paradigm[J].J Clin Endocrinol Metab.2004 Nov;89(l l):5729-37.
[88]Fleisher-Berkovich S,Rimon G,Danon A.Modulation of endothelial prostaglandin synthesis by corticotropin releasing factor and antagonists[J].Eur J Pharmacol.1998 353:297-302.
[89]Udelsman R,Harwood JP,Millan MA,et al.Functional corticotrophin releasing factor receptors in the primate peripheral sympathetic nervous system[J].Nature.1986 319:147-150.
[90]Theoharides TC,Singh LK,Boucher W,et al.Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability,a possible explanation for its proinflammatory effects[J].Endocrinology.1998 139:403-13.
[91].Webster EL,Tracey DE,Jutila MA,Wolfe Jr SA,De Souza EB.Corticotropin-releasing factor receptors in mouse spleen:identification of receptorbearing cells as resident macrophages[J].Endocrinology.1990 127:440-452.
[92]Kawahito Y,Sano H,Mukai S,et al.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut 1995;37:544-551.
[93]Liu S,Gao N,Hu HZ,et al.Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system[J].J Comp Neurol.2006 Jan 1;494(1):63-74.
[94]Hanani M,Wood JD.Corticotropin-releasing hormone excites myenteric neurons in the guinea-pig small intestine[J].Eur J Pharmacol 1992;211:23-27.
[95]Aird F,Clevenger CV,Prystowsky MB,Redei E.Corticotropinreleasing factor mRNA in rat thymus and spleen[J],Proc Natl Acad Sci USA 1993;90:7104-7108.
[96]Kawahito Y,Sano H,Kawata M,Yuri K,Mukai S,Yamamura Y,et al.Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon[J].Gastroenterology 1994;106:859-65.
[97]Scha'fer M,Mousa SA,Stein C.Corticotropin-releasing factor in antonociception and inflammation[J].Eur J Pharmacol 323:1-10,1997.
[98]Chatzaki E,Murphy BJ,Wang L,et al.Differential profile of CRF receptor distribution in the rat stomach and duodenum assessed by newly developed CRF receptor antibodies[J].J Neurochem.2004 Jan;88(l):l-11.
[99]Chatzaki E,Crowe PD,Wang L,Million M,Tache Y,and Grigoriadis DE.CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon[J].J Neurochem 2004;90:309-316.
[100]Liu S,Gao X,Gao N,Wang X,et al.Expression of type 1 corticotropin-releasing factor receptor in the guinea pig enteric nervous system[J].J Comp Neurol 2005;481:284-98.
[101]Santos J,Saunders PR,Hanssen NPM,et al.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[102]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,BhaskarKR,Nikulasson ST,Kornetsky C,and Pothoulakis C.Acute stress causes mucin release from rat colon:role of corticotrophin releasing factor and mast cells[J],Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[103]Wallon C,Yang PC,Keita AV,Ericson AC,McKay DM,Sherman PM,Perdue MH,S?derholm JD.Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro[J].Gut.2008 Jan;57(l):50-8.Epub 2007 May 24.
[104]Ferrier L,Mazelin L,Cenac N,et al.Stress-induced disruption of colonic epithelial barrier:role of interferon-gamma and myosin light chain kinase in mice[J].Gastroenterology 2003;125,795-804.
[105]Barreau F,Carrier C,Leveque M,Ferrier L,Moriez R,Laroute V,Rosztoczy A,Fioramonti J,Bueno L.Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation corticotrophin-releasing factor and nerve growth factor interplay[J].J Physiol.2007 Apr l;580(Pt l):347-56.Epub 2007 Jan 18.
[106]Castagliudo I,Leeman SE,Bartolak-Suki E et al.A neurotensin antagonist,SR 48692,inhibits colonic response to immobilization stress in rats[J],Proc.Natl Acad.Sci.USA 1996;93 12 611-15.
[107]Soderholm JD,Perdue MH.Stress and intestinal barrier function[J].Am.J.Physiol.Gastrointest.Liver Physiol.2001;280:G7-G13.
[108]Santos J,Yang PC,Soderholm JD,Benjamin M,Perdue MH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 2001;48:630-6.
[109]Million M,Tache?Y,and Anton P.Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis:protective role of brain CRF[J].Am J Physiol Gastrointest Liver Physiol 1999;276:G1027-G1036.
[110]Martinez V,Wang L,Rivier J,Grigoriadis D,Tache Y.Central CRF,urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice[J].J Physiol.2004 Apr l;556(Ptl):221-34.
[111]Tache Y,Martinez V,Million M,Rivier J.Corticotropin-releasing factor and the brain gut motor response to stress[J].Can.J.Gastroenterol.1999;13 (Suppl.A):18A-25A.
[112]Monnikes H,Tebbe JJ,Hildebrandt M,et al.Role of stress in functional gastrointestinal disorders.Evidence for stress-induced alterations in gastrointestinal motility and sensitivity[J].Dig Dis.2001;19(3):201-11.
[113]Tache Y,Martinez V,Wang L,et al.CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscero sensitivity:imp lications for irritable bowel syndrome[J].Br J Pharm acol,2004,141 (8):1321-30.
[114]Sagami Y,Shimada Y,Tayama J,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[115]Dinan TG,Quigley EM,Ahmed SM,et al.Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as a potential biomarker?[J].Gastroenterology 2006;130:304-11.
[116]Smith SR,de Jonge L,Pellymounter M,et al.Peripheral Administration of Human Corticotropin-Releasing Hormone:A Novel Method to Increase Energy Expenditure and Fat Oxidation in Man[J].J Clin Endocrinol Metab.2001 May;86(5):1991-8.
[117]-Grunt M,Glaser J,Schmidhuber H,et al.Effects of corticotropin-releasing factor on isolated rat heart activity[J].Am J Physiol.1993 Apr;264(4 Pt 2):H1124-9.
[118]Kanamoto K,Urdanda A,Rivier J.et al.Intravenous urocortin II induced gastroprotection and gastric hyperemia in anesthetized rats:role of CRF receptor 2[J].Gastroenterology 2001 122.A-13.
[119]Gutkowska J,Jankowski M,Mukaddam-Daher,et al.Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats[J].Proc Natl Acad Sci USA.2000 January 4;97(1):483-488.
[120]Tache Y,Martinez V,Million M,and Wang L.Stress and the Gastrointestinal Tract.III.Stress-related alterations of gut motor function:role of brain corticotropin-releasing factor receptors[J].Am J Physiol Gastrointest Liver Physiol 280:G173-G177,2001.
[121]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].2004;16(suppl l):137-42.
[122]Saunders PR,Santos J,Hanssen NP,Yates D,Groot JA,Perdue MH.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci 2002;47:208-215.
[123]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,Bhaskar KR,Nikulasson ST,et al.Acute stress causes mucin release from ratcolon:role of corticotropin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[124]Weiner H.Use of animal models in peptic ulcer disease[J].Psychosom Med 1996;58:524-545.
[125]Nakane T,Kanie N,Audhya T,Hollander CS.The effects of centrally administered neuropeptides on the development of gastric lesions in the rat[J].Life Sci 1985;36:1197-1203.
[126]Ray A,Henke PG,Gulati K,Sen P.The amygdaloid complex,corticotrophin releasing factor and stress-induced gastric ulcerogenesis in rats[J].Brain Res 1993;624:286-290.
[127]Gunion MW,TachS Y.Gastric mucosal damage is inhibited by intraventromedial hypothalamic corticotropin-releasing factor[J].Soc Neurosci Abstr 1986,12:644.
[128]Krahn DD,Wright B,Billington CJ,et al.Exogenous corticotropin-releasing factor inhibits stress-induced gastric ulceration[J].Soc Neurosci Abstr 1986,12:1063.
[129]Esposito P,Chandler N,Kandere K,et al.Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress[J].J Pharmacol Exp Ther.2002 Dec;303(3):1061-6.
[130]Hendryk S,Jedrzejowska-Szypulka H,Josko J,et al.Influence of the corticotropin releasing hormone(CRH) on the brain-blood barrier permeability in cerebral ischemia in rats[J].J Physiol Pharmacol.2002 Mar;53(1):85-94.
[131]Martins JM,Banks WA,Kastin AJ.Transport of CRH from mouse brain directly affects peripheral production of beta-endorphin by the spleen[J].Am J Physiol 1997;273:E1083-E1089.
[132]Martins JM,Kastin AJ,Banks WA.Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone[J].Neuroendocrinology 1996;63:338-348.
[1]Bhatia V,Tandon RK.Stress and the gastrointestinal tract[J].J Gastroenterol Hepatol.2005 Mar;20(3):332-9.
[2]Lennard DE,Eckert WA,Merchenthaler I.Corticotropin—releasing hormone neurons in the paraventricular nucleus project to the external zone of the median eminence:a study combining retrograde labeling with immunocytochemistry[J].J Neuroendocrine!,1993,5 (2):175-181.
[3]Spiess J,Rivier J,Rivier C,et al.Primary structure of corticotrophin — releasing factor from ovine hypothalamus[J].Proc Natl Acad SciUSA,1981,78 (10):6517-6521.
[4]Mayer EA.The neurobiology of stress and gastrointestinal disease[J].Gut 2000;47(6):861-9.
[5]Bakshi V P,Kalin N H.Corticotropin-Releasing hormone and animal models of anxiety:gene-environment Interactions[J].J .B iolPsychiarry,2000,48 (12):1175-98.
[6]Bale TL,Vale WW.CRF and CRF receptors:Role in stress responsivity and other behaviors[J].Ann Rev Pharmacol Toxicol 2004;44:525-557.
[7]Guillemin R.Hypothalamic hormones a.k.a.hypothalamic releasing factors[J].J Endocrinol.2005 Jan;184(1):11-28.
[8]Chen R,Lewis KA,Perrin MH,Vale WW.Expression cloning of a human corticotropin-releasing-factor receptor[J].Proc Natl Acad Sci USA 1993;90:8967-71.
[9]RivestS,Laflamme N.Neuronal activity and neuropeptide gene Transcription in the brains of immune-challenged rats[J],J Neuroendocrinol,1995;7:501-525.
[10]ImakiT,Nahan JL,Rivier C,Sawehenko PE,Vale W.Differential regulation of CRH mRNA in rat brain regions by glucocorticoids and stress[J].J Neurosci,1991;11:585-599.
[11]Owens MJ,Nemeroff CB.Physiology and Pharmacology of Corticotropin-releasing factor[J].Pharmacol Rev,1991:43:425-473.
[12]Dunn AJ,Berridge CW.Physiological and behavioral responses to Corticotropin-releasing factor administration:is CRF a mediator of anxiety or stress responses ?[J].Brain Rev,1990:15:71-100.
[13]Baigent SM.Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response[J].J .Peptides,2001,22 (5):809-20.
[14]Martins JM,Banks WA,Kastin AJ.Transport of CRH from mouse brain directly affects peripheral production of beta-endorphin by the spleen[J].Am J Physiol 1997;273:E1083-E1089.
[15]Martins JM,Kastin AJ,Banks WA.Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone[J].Neuroendocrinology 1996;63:338-348.
[16]Riviere PJ,Pascaud X,Chevalier E,Junien JL.Fedotozine reversal of peritoneal-irritation-induced ileus in rats:Possible peripheral action on sensory afferents[J].J Pharmacol Exp Ther 1994;270:846-850.
[17]Banks WA and Kastin A J.Passage of peptides across the blood-brain barrier:Pathophysiological perspectives[J].Life Sci 1996;59:1923-1943.
[18]Habib KE et al.Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral,neuroendocrine,and autonomic responses to stress in primates[J].Proc Natl Acad Sci U S A 2000;97:6079-6084.
[19]Gilligan PJ,Robertson DW,Zaczek R.Corticotropin releasing factor (CRF) receptor modulators:progress and opportunities for new therapeutic agents[J].J Med Chem 2000;43:1641-1660.
[20]Kawano H.Daikoku S,Shibasaki T.CRF-containing neurons in the rat Hypothalamus:retrograde tracing and immunohistochemical studies[J].J Comp Neurol,1988;272:260-268.
[21]Lennard DE,Eckert WA,Merehenthalerl.CorticotroPin-releasing hormone neurons in the Parlventricular nucleus Project to the external zzone of the median eminence:a study combining retrograde labeling with immunocytochemistry[J].J Neuroendoerinol,1993;5:175-181.
[22]Rivier C,Vale W.Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo[J].Endocrinology.1983 Sep;l 13(3):939-42.
[23]Brown,M.R,Fisher,L.A,1985.Corticotropin-releasing factor:effects on the autonomic nervous system and visceral systems[J].Fed.Proc.44,243-248.
[24]Nijsen MJ,Croiset G,Stam R,et al .The role of the CRH type 1 receptor in autonomic responses to corticotropin-releasing hormone in the rat[J].J Neuropsychopharmacology,2000,22(4):388-399.
[25]Nakade Y,Yoneda M,Nakamura K,et al .Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats[J].Am J Physiol Regul Integr Comp Physiol.2002 Jun;282(6):R1782-8.
[26]Jezova D,Ochedalski T,Glickman M,et al .Central corticotrophin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress[J].J .Neuroscience,1999,94(3):797-802.
[27]Morimoto A,Nakamori T,Morimoto K,Tan N,Murakami N.The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats[J].J Physiol.1993 Jan;460:221-9.
[28]Shafton AD,Fernley RT,McAllen RM.Is CRF a ganglionic transmitter or modulator in the car sudomotor pathway ?[J].Brain Res,1994,652:129-136.
[29]Song C,Earley B,Leonard BE.Behavioral,neurochemical,and immunological responses to CRF administration.Is CRF a mediator of stress?[J].Ann N Y Acad Sci.1995 Dec 29;771:55-72.
[30]Casadevall M,Saperas E.Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor[J].Am J Phy,276 (4):G1016-1026.
[31]Friedman EM,Irwin MR.A role for CRH and the sympathetic nervous system in stress-induced immunosuppression[J].Ann N Y Acad Sci.1995 Dec 29;771:396-418.
[32]Scha'fer M,Mousa SA,Stein C.Corticotropin-releasing factor in antonociception and inflammation[J].Eur J Pharmacol 323:1-10,1997.
[33]Karalis K,Sano H,Redwine J,Listwak S,Wilder RL,Chrousos GP.Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo[J].Science 254:421-423,1991.
[34]Baigent SM.Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response[J].Peptides.2001 May;22(5):809-20.
[35]Webster EL,Barrientos RM,Contoreggi C,et al.Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced arthritis:role of CRH in peripheral inflammation[J].J Rheumatol,2002,29 (6):1252.
[36]McLoon LK,Sandnas AM,Nockleby KJ,et al.Reduction in vesicant-induced cellular inflammation and hyperalgesia by local inj ection of corticotropin releasing factor in rabbit eyelidf J].Inflamm Res,2002,51 (1):16 -23.
[37]Veraksits A,Bileviciute-Ljungar I,Maaroos J,Vasar E,Lundeberg T.Neuronal mechanisms contribute to corticotropin-releasing factor-induced anti-oedema effect in the rat hind paw[J].Neuropeptides.2000 Apr;34(2):129-34.
[38]Kalantaridou SN,Makrigiannakis A,Zoumakis E,Chrousos GP.Reproductive functions of corticotropin-releasing hormone.Research and potential clinical utility of antalarmins (CRH receptor type 1 antagonists)[J].Am J Reprod Immunol.2004 Apr;51(4):269-74.
[39]Elenkov IJ,Chrousos GP.Stress hormones,Thl /Th2 patterns,pro / anti — inflammatory cytokines and susceptibility to disease[J].Trends Endocrinol Metab,1999,10:359-368.
[40]Angeli A,Masera RG,Sartori ML,Fortunati N,Racca S,Dovio A,Staurenghi A,Frairia R.Modulation by cytokines of glucocorticoid action[J].Ann N Y Acad Sci,1999,876(22):210-220.
[41]Tilders FJ,DeRijk RH,Van Dam AM,et al.Activation of the hypothalamus2p ituitary2adrenal axis by bacterial endotoxins:routes and intermediate signals[J].Psychoneuro—endocrinology,1994,19 (2):209-232.
[42]Wang W,Ji P,Riopelle RJ,et al.Functional expression of corticotropin—releasing hormone (CRH) receptor 1 in cultured rat microglia[J].J Neurochem,2002,80 (2):287-294.
[43]Radulovic M,Spiess J.Immunomodulatory role of the corticotropin-releasing factor[J].J .Arch Immunol Ther Exp,2001,49(1):33-38.
[44]Webster EL,Torpy DJ,Elenkov IJ,et al.Corticotropin-releasing hormone and inflammation[J].Ann N Y Acad Sci,1998,840:21-32.
[45]Baigent SM,Lowry PJ.mRNA expression profiles for corticotrophin-releasing factor (CRF),urocortin,CRF receptors and CRF-binding protein in peripheral rat tissues[J].J Mol Endocrinol.2000 Aug;25(l):43-52.
[46]Jessop DS,Harbuz MS,Lightman SL.CRH in chronic inflammatory stress[J].Peptides.2001 May;22(5):803-7.
[47]Raza J,Massoud AF,Hindmarsh PC,et al .Direct effects of corticotrophin-releasing hormone on stimulated growth hormone secretion[J].J .ClinEndocrinol,1998,48(2):217-222.
[48]Tellam DJ,Mohammad YN,Lovejoy DA.Molecular integration of hypothalamo—pituitary—adrenal axis-related neurohormones on the GnRH neuron[J].Biochem Cell Biol,2000,78 (3):205-216.
[49]Arantxa G,Octavi M.Recovery of the hypothalamic-pituitary-adrenal response to stress[J].J Neuroendocrinology,2000,72:114-125.
[50]Lee S,Kim CK,Rivier C.Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B,corticotropin-releasing factor,corticotropin-releasing factor receptor type 1,and vasopressin in the hypothalamus of the intact rat[J].J Neurosci.1999 Sep l;19(17):7640-7.
[51]Cole RL,Sawchenko PE.Neurotransmitter regulation of cellular activation and neuropeptide gene expression in the paraventricular nucleus of the hypothalamus[J].J Neurosci,2002,22(3):959-969.
[52]McCann SM,Antunes RJ,Franci CR.Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection[J].J .Braz J Med Biol Res,2000,33 (10):1121-1131.
[53]De Kloet ER,Vreugdenhil E,Oitzl MS,Jo?ls M.Brain Corticosteroid Receptor Balance in Health and Disease[J].EndocrRev.1998 Jun;19(3):269-301.
[54]Lovenberg TW,Liaw CW,Grigoriadis DE,et al.Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain[J].Proc Natl Acad Sci U S A 1995;92:836-40.
[55]Chang CP,Pearse RV,O'Connell S,et al.Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain[J].Neuron 1993;11:1187-95.
[56]Chen R,Lewis KA,Perrin MH,et al.Expression cloning of a human corticotropin-releasing-factor receptor[J].Proc Natl Acad Sci U S A 1993;90:8967-71.
[57]Aguilera G,Nikodemova M,Wynn P C,et al.Corticotrop in releasing hormone recep tors:two decades later[J].Peptides,2004,25 (3):319-29.
[58]Smith GW,Aubry JM,Dellu F,et al.Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety,impaired stress response,and aberrant neuroendocrine development[J].Neuron 1998;20:1093-102.
[59]Timpl P,Spanagel R,Sillaber I,et al.Impaired stress response and anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1[J].Nat Genet 1998;19:162-6.
[60]MullerM B,Zimmermann S,Sillaber I,et al.Limbic corticotropin—releasing hormone receptorl mediates anxiety —related behavior and hormonal adap tation to stress[J].N at N eurosci,2003,6(10):1100-7.
[61]Maillot C,Million M,Wei JY,et al.Peripheral corticotropin-releasing factor and stress stimulated colonic motor activity involve type 1 receptor in rats[J].Gastroenterology 2000;119:1569-79.
[62]Tache Y,Martinez V,Wang L,et al.CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscero sensitivity:imp lications for irritable bowel syndrome[J].Br J Pharm acol,2004,141(8):1321-30.
[63]Sagami Y,Shimada Y,Tayama J,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[64]GrammatopoulosD K,Chrousos G P.Functional characteristics of CRH recep tors and potential clinical app lications of CRH2receptor antagonists[J].Trends EndocrinolM etab,2002,13(10):436-44.
[65]Bale T L,Contarino A,Smith GW,et al.Mice deficient for corticotrophin-releasing hormone receptor-2 display anxiety-like behavior and are hypersensitive to stress[J].N at Genet,2000,24(4):410-414.
[66]Coste S C,Kesterson R A,Heldwein KA,et al.Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotrophin releasing hormone receptor-2[J].N at Genet,2000,24 (4):403-9.
[67]Hashimoto K,Makino S,Asaba K,Nishiyama M.Physiological roles of corticotropin-releasing hormone receptor type2[J].Endocr J.2001 Feb;48(l):l-9.
[68]Chen C Y,MillionM,Adelson DW,et al.Intracisternal urocortin inhibits vagally stimulated gastric motility in rats:role of CRF2[J],Br J Pharm acol,2002,136 (2):237-47.
[69]Million M,Wang L,Wang Y,Adelson DW.CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats[J].Gut.2006 Feb;55(2):172-81.Epub 2005 Jun 28.
[70]Herringa RJ,Nanda SA,Hsu DT,Roseboom PH,Kalin NH.The effects of acute stress on the regulation of central and basolateral amygdala CRF-binding protein gene expression[J].Brain Res Mol Brain Res.2004 Nov 24;131(l-2):17-25.
[71]D.P.Behan,E.B.De Souza,P.J.Lowry,E.Potter,P.Sawchenko,W.W.Vale.Corticotropin releasing factor (CRF) binding protein:a novel regulator of CRF and related peptides[J].Front.Neuroendocrinol.16 (1995) 362-382.
[72]Kalin NH,Takahashi LK,Chen FL.Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus[J].Brain Res.1994 Sep 5;656(1):182-6.
[73]Selye H.Syndrome produced by diverse nocuous agents[J].Nature 1936;138:32.
[74]Selye H.A syndrome produced by diverse nocuous agents[J].Nature1936;138:32-36.
[75]Schilling D et al.Low seroprevalence of Helicobacter pylori infection in patients with stress ulcer bleeding-a prospective evaluation of patients on a cardiosurgical intensive care unit[J].Intensive Care Med 2000;26:1832-1836.
[76]Spirt MJ.Stress-related mucosal disease:risk factors and prophylactic therapy[J].Clin Ther.2004Feb;26(2):197-213.
[77]Kawakubo K,Fujishima M.Management of gastrointestinal mucosal damage in patients with cerebrovascular disease[J].Nippon Rinsho.2002 Aug;60(8):1573-9.
[78]Bonaz B.Visceral sensitivity perturbation integration in the brain-gut axis in functional digestive disorders[J].J Physiol Pharmacol.2003 Dec;54 Suppl 4:27-42.
[79]Goyal RK,Hirano I.The enteric nervous system[J].N.Engl.J.Med.1996;334:1106-15.
[80]Wallace J,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,1996May;10(7):731-40.
[81]Kawano S,Tsuji S.Role of mucosal blood flow:a conceptional review in gastric mucosal injury and protection[J].J Gastroenterol Hepatol,2000,15(suppl):1.
[82]Saita H,Murakami M,Kita T.Role of mucosal microcirculation in gastric lesions induced by lateral hypothalamic lesions in rats[J].J Gastroenterol Hepatol.1995 Jul-Aug;10(4):371-8.
[83]段义民、李兆申、湛保先等.内皮素在大鼠冷束缚应激性溃疡中的作用[J].胃肠病学 1998,3(3):178-179.
[84]Kobayashi K,Kashimak K,Higuchi K,et al.The mechanisms of gastrointestinal mucosal injury repair[J].Nippon Rinsho,1998,56(9):2215.
[85]Duerksen DR.Stress-related mucosal disease in critically ill patients[J].Best Pract Res Clin Gastroenterol.2003Jun;17(3):327-44.
[86]Anti M,Armuzzi A,Gasbarrini G.Epithelial cell turnover and apoptosis[J].Ital J Gastroenterol Hepatol,1998,30(Suppl 3):S276-278.
[87]Szabo I,Tarnawski AS.Apoptosis in the gastric mucosa:molecular mechanisms,basic and clinical implications[J].J Physiol Pharmacol,2000,51(1):3.
[88]Konturek PC,Brzozowski T,Konturek SJ et al.Apoptosis in gastric mucosa with stress-induced gastric ulcers[J].J Physiol Pharmacol.1999 Jun;50(2):211-25.
[89]李兆申,刘婧,许国铭等.不同抗溃疡药物对应激性溃疡发生发展过程中细胞凋亡的影响[J].胃肠病学2003,8(1):11-14.
[90]Konturek PC,Brzozowski T,Duda A et al.Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis[J].J Physiol Paris.2001Jan-Dec;95(1-6):361-7.
[91]Kern W,Schiefer B,Schwarzenburg J,et al.Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans[J].Neuroendocrinology,1997,65(4):291-298.
[92]Klamut MJ,Keshavarzian A.Stress ulcer[J].J Assoc Acad Minor Phys.1992;3(3):89-94.
[93]Peterson WL.The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress-related mucosal damage[J].Aliment Pharmacol Ther.1995;9 Suppl 1:43-6.
[94]Datta UK.Effect of heat stress on gastro-intestinal motility in young albino rats[J].Indian J Physiol Pharmacol.2001 Apr;45(2):222-6.
[95]Plourde V.Can J Gastroenterol.Stress-induced changes in the gastrointestinal motor system[J].Can J Gastroenterol.1999 Mar;13 Suppl A:26A-31A.
[96]Thomson AB,Keelan M,Thiesen A,et al.Small bowel review:normal physiology part 2[J].Dig Dis Sci.2001Dec:46(12):2588-2607.
[97]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Pharm Sci Technol Today,1999 Jul,2(7):281-287.
[98]van der Hulst RR,von Meyenfeldt MF,van Kreel BK,et al.Gut permeability,intestinal morphology,and nutritional depletion[J].Nutrition.1998 Jan;14(1):1-6.
[99]MacFie J.Enteral versus parenteral nutrition:the significance of bacterial translocation and gut-barrier function[J].Nutrition,2000 Jul-Aug,16(7-8):606-611.
[100]Saunders PR,Kosecka U,McKay DM,et al.Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine[J].Am J Physiol,1994;267(5Pt1);G794-799.
[101]Santos J,Saperas E,Mourelle M,et al.Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats[J].Gastroenterology,1996:111(6):1465-1473.
[102]Madara JL.Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium:physiological rearrangement of tight junctions[J].J Membr Biol,1990:116(2):177-184.
[103]Kiliaan AJ,Saunders PR,Bijlsma PB et al.Stress stimulates transepithelial macromolecular uptake in rat jejunum[J].Am.J.Physiol.Gastrointest.Liver Physiol.1998;275(5 Part 1):G1037-G1044.
[104]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J].Gastroenterology,2000;119(4);1019-1028.
[105]黎介寿.肠衰竭-概念、营养支持与肠粘膜屏障维护中国临床营养杂志[J].中国临床营养杂志,2004;3:155-158.
[106]Soderholm JD,Perdue MH.Stress and gastrointestinal tract.Ⅱ.Stress and intestinal barrier function[J].Am J Physiol Gastrointest Liver Physiol,2001;280(1):G7-G13.
[107]Castagliuolo I,Lamont JT,Qiu B,et al.Acute stress causes mucin release from rat colon:role of corticotropin releasing factor and mast cells[J].Am J Physiol,1996:271(5Pt1):G884-892.
[108]Newson B,Dahlstrom A,Enerback L,et al.Suggestive evidence for a direct innervation of mucosal mast cells[J].Neuroscience,1983,10(2):565-570.
[109]Santos J,Yang PC,Soderholm JD,Benjamin M,Perdue MH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 2001;48:630-6.
[110]Santos J,Saperas E,Nogueiras C et al.Release of mast cell mediators into the jejunum by cold pain stress in humans[J].Gastroenterology 1998;114:640-8.
[111]Santos J,Benjamin M,Yang PC,et al.Chronic stress impairs rato growth and jejunal epithelial barrier function .role of mast cells[J].Am J Physiol,2000,278:G847-G854.
[112]Wilson LM.Baldwin AL.Environmental stress causes mast cell degranulation,endothelial and epithelial changes,and edema in the rat intestinal mucosa[J].Microcirculation,1999;6(3):189-198.
[113]Castagliuolo I,Wershil BK,Karalis K,et al.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol,1998;274(6Ptl)“.G1094-1100.
[114]Barclay GR,Turnberg LA.Effect of psychological stress on salt and water transport in the human jejunum[J],Gastroenterology,1987;93(1):91-97.
[115]Nakane T,Kanie N,Audhya T,Hollander CS.The effects of centrally administered neuropeptides on the development of gastric lesions in the rat[J].Life Sci 1985;36:1197-1203.
[116]Ray A,Henke PG,Gulati K,Sen P.The amygdaloid complex,corticotrophin releasing factor and stress-induced gastric ulcerogenesis in rats[J].Brain Res 1993;624:286-290.
[117]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,Webster EL,McCann SM,Gold PW.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry.2002;7(5):474-83,433.
[118]Castagliudo I,Leeman SE,Bartolak-Suki E et al.A neurotensin antagonist,SR 48692,inhibits colonic response to immobilization stress in rats[J].Proc.Natl Acad.Sci.USA 1996;93 12 611-15.
[119]Santos J,Saunders PR,Hanssen NP et al.Corticotropin releasing hormone mimics stress induced colonic epithelial pathophysiology in the rat[J].Am.J.Physiol.Gastrointest.Liver Physiol.1999;277 (2 Part 1):G391-G399.
[120]Aird F,Clevenger CV,Prystowsky MB,Redei E.Corticotropinreleasing factor mRNA in rat thymus and spleen[J].Proc Natl Acad Sci USA 1993;90:7104-7108.
[121]Kawahito Y,Sano H,Mukai S,Asai K,Kimura S,Yamamura Y,etal.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut 1995;37:544-551.
[122]Liu S,Gao N,Hu H-Z,Wang X,Wang G-D,Fang X,et al.Distribution and chemical coding of corticotropin-releasing factorimmunoreactive neurons in the guinea pig enteric nervous system[J].J Comp Neurol 2006;494:63-74.
[123]Chatzaki E,Crowe PD,Wang L,Million M,Tache Y,and Grigoriadis DE.CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon[J].J Neurochem 2004;90:309-316.
[124]Kawahito Y,Sano H,Kawata M,Yuri K,Mukai S,Yamamura Y,et al.Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon[J].Gastroenterology 1994;106:859-65.
[125]Bale TL.Sensitivity to stress Dysregulation of CRF pathways and disease development[J].Horm Behav.2005 Jun;48(1):1-10.Epub 2005 Mar 17.
[126]Overton JM,Fisher LA.Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats[J].J Autonom Nerv Syst 35:43-52,1991.
[127]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil 2004;16:137-142.
[128]Santos J,Saunders PR,Hanssen NPM,et al.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[129]Saunders PR,Santos J,Hanssen NP,Yates D,Groot JA,Perdue MH.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci 2002;47:208-215.
[130]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,et al.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry 2002;7:474-483.
[131]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,Bhaskar KR,Nikulasson ST,et al.Acute stress causes mucin release from ratcolon:role of corticotropin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[132]Castagliuolo I,Wershil BK,Karalis K,Pasha A,Nikulasson ST,Bisschops C.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol Gastrointest Liver Physiol 1998;274:G1094-G1100.
[133]V.Martinezl and Y.Tache.CRF1 Receptors as a Therapeutic Target for Irritable Bowel Syndrome[J].Current Pharmaceutical Design,2006,12,4071-4088.
[134]Kawahito Y,Sano H,Mukai S.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut.1995 Oct;37(4):544-51.
[135]Saunders PR,Santos J,Hanssen NP,et al.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci,2002;47(1):208-215.
[136]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,BhaskarKR,Nikulasson ST,Kornetsky C,and Pothoulakis C.Acute stress causes mucin release from rat colon:role of corticotrophin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[137]Santos J,Saunders PR,Hanssen NP,Yang PC,Yates D,Groot JA,and Perdue MH.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in therat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[138]Million M,Tache?Y,and Anton P.Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis:protective role of brain CRF[J].Am J Physiol Gastrointest Liver Physiol 1999;276:G1027-G1036.
[139]Soderholm JD,Perdue MH.Stress and intestinal barrier function[J].Am.J.Physiol.Gastrointest.Liver Physiol.2001;280:G7-G13.
[140]Tache Y,Martinez V,Million M,and Wang L.Stress and the Gastrointestinal Tract.III.Stress-related alterations of gut motor function:role of brain corticotropin-releasing factor receptors[J].Am J Physiol Gastrointest Liver Physiol 2001;280:G173-G177.
[141]Eutamene H,Theodorou V,Fioramonti J,Bueno L.Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats[J].J Physiol.2003 Dec 15;553(Pt3):959-66.
[142]Ferrier L,Mazelin L,Cenac N,et al.Stress-induced disruption of colonic epithelial barrier:role of interferon-gamma and myosin light chain kinase in mice[J].Gastroenterology 2003;125,795-804.
[143]Barreau F,Carrier C,Leveque M,Ferrier L,Moriez R,Laroute V,Rosztoczy A,Fioramonti J,Bueno L.Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation corticotrophin-releasing factor and nerve growth factor interplay[J].J Physiol.2007 Apr l;580(Pt l):347-56.Epub 2007 Jan 18.
[144]Wallon C,Yang PC,Keita AV,Ericson AC,McKay DM,Sherman PM,Perdue MH,S?derholm JD.Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro[J].Gut.2008 Jan;57(l):50-8.Epub 2007 May 24.
[145]Kokkotou E,Torres D,Moss AC,O'Brien M,Grigoriadis DE,Karalis K,Pothoulakis C.Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses[J].J Immunol.2006 Sep 1;177(5):3355-61.
[146]Martinez V,Wang L,Rivier J,Grigoriadis D,Tache Y.Central CRF,urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice[J].J Physiol.2004 Aprl;556(Pt l):221-34.
[147]Tache Y,Martinez V,Million M,Rivier J.Corticotropin-releasing factor and the brain gut motor response to stress[J].Can.J.Gastroenterol.1999;13 (Suppl.A):18A-25A.
[148]Monnikes H,Tebbe JJ,Hildebrandt M,et al.Role of stress in functional gastrointestinal disorders.Evidence for stress-induced alterations in gastrointestinal motility and sensitivity[J].Dig Dis.2001;19(3):201-11.
[149]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil.2004 Apr;16 Suppl 1:137-42.
[150]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].2004;16(suppl 1):137-42.
[151]Lewis MW,Hermann GE,Rogers RC,and Travagli RA.In vitro and in vivo analysis of the effects of corticotropin releasing factor on rat dorsal vagal complex[J].J Physiol 543:135-146,2002.
[152]Tsukamoto K,Nakade Y,Mantyh C,Ludwig K,Pappas TN,and Takahashi T.Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats[J].Am J Physiol Regul Integr Comp Physiol 2006;290:R1537-R1541.
[153]Richard C.Rogers,Gerlinda E.Hermann,and R.Alberto Travagli.Stress and the colon:central-vagal or direct peripheral effect of CRF?[J].Am J Physiol Regul Integr Comp Physiol 2006;290:R1535-R1536.
[154]Sagami Y,Shimada Y,Tayama J,Nomura T,Satake M,Endo Y,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[155]Shin Fukudo.Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation[J].J Gastroenterol 2007;42[Suppl ⅩⅦ]:48-51.
[156]Nozu T,Kudaira M.Corticotropin-releasing factor induces rectal hypersensitivity after repetitive painful rectal distention in healthy humans[J].J Gastroenterol.2006 Aug;41(8):740-4.
[157]Greenwood-Van Meerveld B,Johnson AC,Cochrane S,Schulkin J,Myers DA.Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats[J].Neurogastroenterol Motil.2005 Jun;17(3):415-22.
[158]Trimble N,Johnson AC,Foster A,Greenwood-van Meerveld B.Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity[J].Neurogastroenterol Motil.2007 Sep;19(9):754-60.
[2]Spiess J,Rivier J,Rivier C,et al.Primary structure of corticotrophin-releasing factor from ovine hypothalamus[J].Proc Natl Acad SciUSA,1981,78 (10):6517-6521.
[3]Mayer EA.The neurobiology of stress and gastrointestinal disease[J].Gut 2000;47(6):861-9.
[4]Bakshi V P,Kalin N H.Corricotropin-Releasing hormone and animal models of anxiety:gene-environment Interactions[J].J .B iolPsychiatry,2000,48 (12):1175-98.
[5]Bale TL,Vale WW.CRF and CRF receptors:Role in stress responsivity and other behaviors[J].Ann Rev Pharmacol Toxicol 2004;44:525-557.
[6]Meddings JB,Sutherland LR,Byles NI.Sucrose:a novel permeability marker for gastroduodenal disease.Gastroenterology[J].Gastroenterology.1993 Jun;104(6):1619-26.
[7]Sutherl LR,Verhoef M,Wallace JL,et al.A simple,non-invasive marker of gastric damage:sucrose permeability[J].Lancet,1994;343:998-1000.
[8]Tsunooka N,Maeyama K,Hamada Y,et al.Bacterial translocation secondary to small intestinal mucosal ischemia during cardiopulmonary bypass.Measurement by diamine oxidase and peptidoglycan[J].Eur J Cardiothorac Surg.2004 Feb;25(2):275-80.
[9]Johnston SD,Smye M,Watson RP.Intestinal permeability tests in coeliac disease[J].Clin Lab.2001;47(3-4):143-50.
[10]Magnotti LJ,Deitch EA.Burns,bacterial translocation,gut barrier function,and failure[J].J Burn Care Rehabil.2005 Sep-Oct;26(5):383-91.
[11]Charmandari E,Tsigos C,Chrousos G.et al.Endocrinology of the stress response[J].Annu Rev Physiol.2005;67:259-84.
[12]Dantzer R,Mormede P.Stress in farm animals:a need forreevaluation[J].J Anim Sci.1983 Jul;57(l):6-18.
[13]Fibiger W,Singer G,Miller AJ,et al.Cortisol and catecholamines changes as functions of time-of-day and self-reported mood[J].Neurosci Biobehav Rev.1984 Winter;8(4):523-30.
[14]M.Hay,M.C.Meunier-Salaun,F.Brulaud,et al.Assessment of hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity in pregnant sows through the measurement of glucocorticoids and catecholamines in urine[J].J Anim Sci 2000.78:420-428.
[15]Koizumi J,Yoshida Y,Nakazwa F,et al.Experimental studies of ischemic brain edema:1 .A new experimental mode of cerebral embolism in rats in which recirlation can be introduced in the ischemic area[J].Stroke,1986,8:128.
[16]Davies NM,Corrigan BW,Jamali F.Sucrose urinary excretion in the rat measured using a simple assay:a model of gastroduodenal permeability[J].Pharm Res.1995 Nov;12(l l):1733-6.
[17]Morimoto A,Nakamori T,Morimoto K,Tan N,Murakami N.The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats[J].Journal of Physiology 1993;460,pp.221-229.
[18]Santos J,Saunders PR,Hanssen NP,Yang PC,Yates D,Groot JA,and Perdue MH.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in therat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[19]Javier Santos,Paul R.Saunders,Nico P.M.Hanssen,et al .Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[20]PaxinosG,WatsonC.The Rat Brain in Stereotaxie Coordinates,4th edition[J].Academie Press,New York,1998.
[21]Longa EZ,Weinstein PR.Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20 (1):84-91.
[22]Chiu CJ,McArdle AH,Brown R,et al.Intestinal mucosal lesion in low-flow states.I.A morphological,hemodynamic,and metabolic reappraisal[J].Arch Surg,1970;101:478-483.
[23]Selye H.A syndrome produced by diverse nocuous agents[J].Nature1936;138:32-36.
[24]Thomson AB,Keelan M,Thiesen A,et al.Small bowel review,normal physiology part 2[J].Dig Dis Sci.2001 Dec;46(12):2588-2607.
[25]Schilling D et al.Low seroprevalence of Helicobacter pylori infection in patients with stress ulcer bleeding-a prospective evaluation of patients on a cardiosurgical intensive care unit[J].Intensive Care Med 2000;26:1832-1836.
[26]O'Donnell MJ,Kapral MK,Fang J,et al.Gastrointestinal bleeding after acute ischemic stroke[J].Neurology.2008 Aug 26;71(9):650-5.
[27]Deitch EA.Bacterial translocation or lymphatic drainage of toxic products from the gut:what is important in human beings?[J].Surgery.2002 Mar,131(3):241-244.
[28]Spirt MJ.Stress-related mucosal disease:risk factors and prophylactic therapy[J].Clin Ther.2004 Feb:26(2):197-213.
[29]Steinberg KP.Stress-related mucosal disease in the critically ill patient:risk factors and strategies to prevent stress-related bleeding in the intensive care unit[J].Crit Care Med.2002 Jun;30(6Suppl):S362-4.
[30]Stollman N.Metz DC.Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients[J].Crit Care.2005 Mar;20(l):35-45.
[31]Bhatia V,Tandon RK.Stress and the gastrointestinal tract[J].J Gastroenterol Hepatol.2005 Mar;20(3):332-9.
[32]Caso JR,Leza JC,Menchen L.The effects of physical and psychological stress on the gastro-intestinal tract:lessons from animal models[J].Curr Mol Med.2008 Jun;8(4):299-312.
[33]Bederson JB,Pitts LH,TsujiM,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke,1986,17 (3) .472-476.
[34]Alexis NE.Dietrich WD,Green EJ,et al.Nonocclusive common carotid artery thrombosis in the rat results in reversible sensorimotor and cognitive behavioral deficits[J].Stroke,1995,26 (12):2338-2346.
[35]Liu XG,Xu LN.A rat middle cerebral artery thrombosis model for evaluation of thrombolytic and antithrombotic agents[J].ActaPharmSin,1995,30 (9):662-667.
[36]Wang W,Dong WW,Fu YG,et al.The MCA occlusion and reperfusion model induced by photochemico!ogy[J].ChinJ NeuruMent Dis,1996,22 (1):27-30.
[37]Saunders PR,Kosecka U,McKay DM,et al.Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine[J].Am J Physiol,1994;267(5Ptl);G794-799.
[38]Yoshimura H,Kan N,Ogawa N.Preventive and curative effects of prostaglandins on stress ulcer in rats[J].Dig Dis Sci 34:436-444,1989.
[39]Wallace J,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,1996 May;10(7):731-40.
[40]Levine BA.Pathophysiology and mechanisms of stress ulcer injury[J].Pharmacotherapy.1987;7(6 Pt 2):90S-94S.
[41]Yabana T,Yachi A.Stress-induced vascular damage and ulcer[J].Dig Dis Sci.1988 Jun;33(6):751-61.
[42]Konturek PC,Brzozowski T,Konturek SJ,et al.Apoptosis in gastric mucosa with stress-induced gastric ulcers[J].J Physiol Pharmacol.1999 Jun;50(2):211-25.
[43]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Pharm Sci Technol Today,1999 Jul,2(7):281-287.
[44]van der Hulst RR,von Meyenfeldt MF,van Kreel BK,et al.Gut permeability,intestinal morphology,and nutritional depletion[J].Nutrition.1998 Jan;14(l):l-6.
[45]MacFie J.Enteral versus parenteral nutrition:the significance of bacterial translocation and gut-barrier function[J].Nutrition,2000 Jul-Aug,16(7-8):606-611.
[46]Santos J,Saperas E,Mourelle M,et al.Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats[J].Gastroenterology,1996;111 (6);1465-1473.
[47]Santos J,Yang PC,So'derholm JD,Benjamin M,and PerdueMH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 48:630-636,2001.
[48]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J],Gastroenterology,2000;119(4);1019-1028.
[49]Madara JL.Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium:physiological rearrangement of tight junctions[J].J Membr Biol,1990;116(2);177-184.
[50]Kiliaan AJ,Saunders PR,Bijlsma PB et al.Stress stimulates transepithelial macromolecular uptake in rat jejunum[J].Am.J.Physiol.Gastrointest.Liver Physiol.1998;275 (5 Part 1):G1037-G1044.
[51]Wilson,LM,and Baldwin AL.Environmental stress causes mast cell degranulation,endothelial and epithelial changes,and edema in the rat intestinal mucosa[J].Microcirculation 1999,6:189-198.
[52]Spitz,JC,Ghandi S,Taveras M,Aoys E,and Alverdy JC.Characteristics of the intestinal epithelial barrier during dietary manipulation and glucocorticoid stress[J].Crit Care Med 1996,24:635-641.
[53]So'derholm JD,Yang PC,Ceponis P,et al.Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine[J].Gastroenterology.2002 Oct;123(4):1099-108.
[54]Bailey,MT,and Coe CL.Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys[J].Dev Psychobiol 1999,35:146-155.
[55]Castagliuolo I,Lamont JT,Qiu B,et al.Acute stress causes mucin release from rat colon:role of corticotropin releasing factor and mast cells[J].Am J Physiol,1996;271(5Ptl):G884-892.
[56]Coplan JD,Andrews MW,Rosenblum LA,et al.Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors:implications for the pathophysiology of mood and anxiety disorders[J].Proc Natl Acad Sci USA 1996 93:1619-1623.
[57]Bakshi VP,KalinNH.Corticotropin-releasing hormone and animal models of anxiety:gene-environment interactions[J].Biol Psychiatry 2000 48:1175-1198.
[58]Banks WA and Kastin A J.Passage of peptides across the blood-brain barrier:Pathophysiological perspectives[J].Life Sci 1996;59:1923-1943.
[59]Riviere PJ,Pascaud X,Chevalier E,Junien JL.Fedotozine reversal of peritoneal-irritation-induced ileus in rats:Possible peripheral action on sensory afferents[J].J Pharmacol Exp Ther 1994;270:846-850.
[60]Habib KE et al.Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral,neuroendocrine,and autonomic responses to stress in primates[J].Proc Natl Acad Sci U S A 2000;97:6079-6084.
[61]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,et al.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry 2002;7:474-483.
[62]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil 2004;16:137-142.
[63]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J].Gastroenterology.2000 Oct;119(4):1019-28.
[64]Dunn AJ,Berridge CW.Physiological and behavioral responses to corticotropin-releasing factor administration:is CRF a mediator of anxiety or stress responses?[J].Brain Res Rev 1990;15:71-100.
[65]Valentino RJ,Page M,Van Bockstaele E,et al .Corticotropin-releasing factor innervation of the locus coeruleus region:distribution of fibers and sources of input[J].Neuroscience.1992;48(3):689-705.
[66]Valentino RJ,Foote SL,Aston-Jones G.Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus[J].Brain Res.1983 Jul 4;270(2):363-7.
[67]Jezova D,Ochedalski T,Glickman M,et al .Central corticotrophin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress[J].J .Neuroscience,1999,94(3):797-802.
[68]Hank P.Jedemal and Anthony A.Grace.Corticotropin-Releasing Hormone Directly Activates Noradrenergic Neurons of the Locus Ceruleus Recorded In Vitro[J].J Neuroscience,2004 24(43):9703-9713.
[69]Sawchenko PE,Swanson LW.The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat[J].Brain Res.1982 Nov;257(3):275-325.
[70]Overton JM,Fisher LA.Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats[J].J Auton Nerv Syst.1991 Jul;35(l):43-51.
[71]McCann SM,Antunes RJ,Franci CR.Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection[J].J .Braz J Med Biol Res,2000,33 (10):1121-1131.
[72]Lyons MK,Anderson RE,Meyer FB.Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury[J].Brain Res.1991 Apr 5;545(l-2):339-42.
[73]Strijbos PJ,Relton JK,Rothwell NJ.Corticotrophin-releasing factor antagonist inhibits neuronal damage induced by focal cerebral ischaemia or activation of NMDA receptors in the rat brain[J].Brain Res.1994 Sep 12;656(2):405-8.
[74]Choi DI,Park SK,Kim HS,et al.Expression of corticotropin releasing factor,but not its binding protein,in CA1 pyramidal cells of gerbil hippocampus following transient ischemia[J],Brain Res.2001 Apr 27;899(l-2):255-9.
[75]Wong ML,Loddick SA,Bongiorno PB,et al.Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala[J].Neuroreport.1995 Sep 11;6(13):1785-8.
[76]Mackay KB,Bozigian H,Grigoriadis DE,et al.Neuroprotective effects of the CRFI antagonist R121920 after permanent focal ischemia in the rat[J].J Cereb Blood Flow Metab.2001 Oct;21(10):1208-]4.
[77]Habib KE,Negro PJ,Sciullo D,Dib A,Gold PW.Protective role of the sympathoadrenal system against stress-induced gastric mucosal injury in the rat[J].Gastroenterology 1999;116:G0783.
[78]Hernandez DE.Neuroendocrine mechanisms of stress ulceration:focus on thyrotropin-releasing hormone[J].Life Sci 1986;39:279-296.
[79]Grijalva CV,Novin D.The role of the hypothalamus and dorsal vagal complex in gastrointestinal function and pathophysiology[J].Ann N Y Acad Sci 1990;597:207-222.
[80]Weiner H.From simplicity to complexity (1950-1990):the case of peptic ulceration-Ⅱ.Animal studies[J].Psychosom Med 1991;53:491-516.
[81]Weichert RF,3rd,Ellison JP,Woolverton WC,Drapanas T.Postvagotomy serotonin depletion in mucosal mast cells of the rat stomach[J].Surg Forum 1970;21:318-320.
[82]Williams CL,Villar RG,Peterson JM,Burks TF.Stress-induced changes in intestinal transit in the rat:a model for irritable bowel syndrome[J].Gastroenterology 1988;94:611-621.
[83]Soderholm JD,Yates DA,Gareau MG,et al.Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress[J].Am J Physiol Gastrointest Liver Physiol.2002 Dec;283(6):G1257-63.
[84]V.Martinez! and Y.Tache.CRFI Receptors as a Therapeutic Target for Irritable Bowel Syndrome[J].Current Pharmaceutical Design,2006,12,4071-4088.
[85]Castagliuolo I,Wershil BK,Karalis K,Pasha A,Nikulasson ST,Bisschops C.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol Gastrointest Liver Physiol 1998;274:G1094-G1100.
[86]Fukudo S.Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation[J].J Gastroenterol.2007 Jan;42 Suppl 17:48-51.
[87]Ayala AR,Pushkas J,Higley JD,et al.Behavioral,Adrenal,and Sympathetic Responses to Long-Term Administration of an Oral Corticotropin-Releasing Hormone Receptor Antagonist in a Primate Stress Paradigm[J].J Clin Endocrinol Metab.2004 Nov;89(l l):5729-37.
[88]Fleisher-Berkovich S,Rimon G,Danon A.Modulation of endothelial prostaglandin synthesis by corticotropin releasing factor and antagonists[J].Eur J Pharmacol.1998 353:297-302.
[89]Udelsman R,Harwood JP,Millan MA,et al.Functional corticotrophin releasing factor receptors in the primate peripheral sympathetic nervous system[J].Nature.1986 319:147-150.
[90]Theoharides TC,Singh LK,Boucher W,et al.Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability,a possible explanation for its proinflammatory effects[J].Endocrinology.1998 139:403-13.
[91].Webster EL,Tracey DE,Jutila MA,Wolfe Jr SA,De Souza EB.Corticotropin-releasing factor receptors in mouse spleen:identification of receptorbearing cells as resident macrophages[J].Endocrinology.1990 127:440-452.
[92]Kawahito Y,Sano H,Mukai S,et al.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut 1995;37:544-551.
[93]Liu S,Gao N,Hu HZ,et al.Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system[J].J Comp Neurol.2006 Jan 1;494(1):63-74.
[94]Hanani M,Wood JD.Corticotropin-releasing hormone excites myenteric neurons in the guinea-pig small intestine[J].Eur J Pharmacol 1992;211:23-27.
[95]Aird F,Clevenger CV,Prystowsky MB,Redei E.Corticotropinreleasing factor mRNA in rat thymus and spleen[J],Proc Natl Acad Sci USA 1993;90:7104-7108.
[96]Kawahito Y,Sano H,Kawata M,Yuri K,Mukai S,Yamamura Y,et al.Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon[J].Gastroenterology 1994;106:859-65.
[97]Scha'fer M,Mousa SA,Stein C.Corticotropin-releasing factor in antonociception and inflammation[J].Eur J Pharmacol 323:1-10,1997.
[98]Chatzaki E,Murphy BJ,Wang L,et al.Differential profile of CRF receptor distribution in the rat stomach and duodenum assessed by newly developed CRF receptor antibodies[J].J Neurochem.2004 Jan;88(l):l-11.
[99]Chatzaki E,Crowe PD,Wang L,Million M,Tache Y,and Grigoriadis DE.CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon[J].J Neurochem 2004;90:309-316.
[100]Liu S,Gao X,Gao N,Wang X,et al.Expression of type 1 corticotropin-releasing factor receptor in the guinea pig enteric nervous system[J].J Comp Neurol 2005;481:284-98.
[101]Santos J,Saunders PR,Hanssen NPM,et al.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[102]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,BhaskarKR,Nikulasson ST,Kornetsky C,and Pothoulakis C.Acute stress causes mucin release from rat colon:role of corticotrophin releasing factor and mast cells[J],Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[103]Wallon C,Yang PC,Keita AV,Ericson AC,McKay DM,Sherman PM,Perdue MH,S?derholm JD.Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro[J].Gut.2008 Jan;57(l):50-8.Epub 2007 May 24.
[104]Ferrier L,Mazelin L,Cenac N,et al.Stress-induced disruption of colonic epithelial barrier:role of interferon-gamma and myosin light chain kinase in mice[J].Gastroenterology 2003;125,795-804.
[105]Barreau F,Carrier C,Leveque M,Ferrier L,Moriez R,Laroute V,Rosztoczy A,Fioramonti J,Bueno L.Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation corticotrophin-releasing factor and nerve growth factor interplay[J].J Physiol.2007 Apr l;580(Pt l):347-56.Epub 2007 Jan 18.
[106]Castagliudo I,Leeman SE,Bartolak-Suki E et al.A neurotensin antagonist,SR 48692,inhibits colonic response to immobilization stress in rats[J],Proc.Natl Acad.Sci.USA 1996;93 12 611-15.
[107]Soderholm JD,Perdue MH.Stress and intestinal barrier function[J].Am.J.Physiol.Gastrointest.Liver Physiol.2001;280:G7-G13.
[108]Santos J,Yang PC,Soderholm JD,Benjamin M,Perdue MH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 2001;48:630-6.
[109]Million M,Tache?Y,and Anton P.Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis:protective role of brain CRF[J].Am J Physiol Gastrointest Liver Physiol 1999;276:G1027-G1036.
[110]Martinez V,Wang L,Rivier J,Grigoriadis D,Tache Y.Central CRF,urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice[J].J Physiol.2004 Apr l;556(Ptl):221-34.
[111]Tache Y,Martinez V,Million M,Rivier J.Corticotropin-releasing factor and the brain gut motor response to stress[J].Can.J.Gastroenterol.1999;13 (Suppl.A):18A-25A.
[112]Monnikes H,Tebbe JJ,Hildebrandt M,et al.Role of stress in functional gastrointestinal disorders.Evidence for stress-induced alterations in gastrointestinal motility and sensitivity[J].Dig Dis.2001;19(3):201-11.
[113]Tache Y,Martinez V,Wang L,et al.CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscero sensitivity:imp lications for irritable bowel syndrome[J].Br J Pharm acol,2004,141 (8):1321-30.
[114]Sagami Y,Shimada Y,Tayama J,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[115]Dinan TG,Quigley EM,Ahmed SM,et al.Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome:plasma cytokines as a potential biomarker?[J].Gastroenterology 2006;130:304-11.
[116]Smith SR,de Jonge L,Pellymounter M,et al.Peripheral Administration of Human Corticotropin-Releasing Hormone:A Novel Method to Increase Energy Expenditure and Fat Oxidation in Man[J].J Clin Endocrinol Metab.2001 May;86(5):1991-8.
[117]-Grunt M,Glaser J,Schmidhuber H,et al.Effects of corticotropin-releasing factor on isolated rat heart activity[J].Am J Physiol.1993 Apr;264(4 Pt 2):H1124-9.
[118]Kanamoto K,Urdanda A,Rivier J.et al.Intravenous urocortin II induced gastroprotection and gastric hyperemia in anesthetized rats:role of CRF receptor 2[J].Gastroenterology 2001 122.A-13.
[119]Gutkowska J,Jankowski M,Mukaddam-Daher,et al.Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats[J].Proc Natl Acad Sci USA.2000 January 4;97(1):483-488.
[120]Tache Y,Martinez V,Million M,and Wang L.Stress and the Gastrointestinal Tract.III.Stress-related alterations of gut motor function:role of brain corticotropin-releasing factor receptors[J].Am J Physiol Gastrointest Liver Physiol 280:G173-G177,2001.
[121]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].2004;16(suppl l):137-42.
[122]Saunders PR,Santos J,Hanssen NP,Yates D,Groot JA,Perdue MH.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci 2002;47:208-215.
[123]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,Bhaskar KR,Nikulasson ST,et al.Acute stress causes mucin release from ratcolon:role of corticotropin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[124]Weiner H.Use of animal models in peptic ulcer disease[J].Psychosom Med 1996;58:524-545.
[125]Nakane T,Kanie N,Audhya T,Hollander CS.The effects of centrally administered neuropeptides on the development of gastric lesions in the rat[J].Life Sci 1985;36:1197-1203.
[126]Ray A,Henke PG,Gulati K,Sen P.The amygdaloid complex,corticotrophin releasing factor and stress-induced gastric ulcerogenesis in rats[J].Brain Res 1993;624:286-290.
[127]Gunion MW,TachS Y.Gastric mucosal damage is inhibited by intraventromedial hypothalamic corticotropin-releasing factor[J].Soc Neurosci Abstr 1986,12:644.
[128]Krahn DD,Wright B,Billington CJ,et al.Exogenous corticotropin-releasing factor inhibits stress-induced gastric ulceration[J].Soc Neurosci Abstr 1986,12:1063.
[129]Esposito P,Chandler N,Kandere K,et al.Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress[J].J Pharmacol Exp Ther.2002 Dec;303(3):1061-6.
[130]Hendryk S,Jedrzejowska-Szypulka H,Josko J,et al.Influence of the corticotropin releasing hormone(CRH) on the brain-blood barrier permeability in cerebral ischemia in rats[J].J Physiol Pharmacol.2002 Mar;53(1):85-94.
[131]Martins JM,Banks WA,Kastin AJ.Transport of CRH from mouse brain directly affects peripheral production of beta-endorphin by the spleen[J].Am J Physiol 1997;273:E1083-E1089.
[132]Martins JM,Kastin AJ,Banks WA.Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone[J].Neuroendocrinology 1996;63:338-348.
[1]Bhatia V,Tandon RK.Stress and the gastrointestinal tract[J].J Gastroenterol Hepatol.2005 Mar;20(3):332-9.
[2]Lennard DE,Eckert WA,Merchenthaler I.Corticotropin—releasing hormone neurons in the paraventricular nucleus project to the external zone of the median eminence:a study combining retrograde labeling with immunocytochemistry[J].J Neuroendocrine!,1993,5 (2):175-181.
[3]Spiess J,Rivier J,Rivier C,et al.Primary structure of corticotrophin — releasing factor from ovine hypothalamus[J].Proc Natl Acad SciUSA,1981,78 (10):6517-6521.
[4]Mayer EA.The neurobiology of stress and gastrointestinal disease[J].Gut 2000;47(6):861-9.
[5]Bakshi V P,Kalin N H.Corticotropin-Releasing hormone and animal models of anxiety:gene-environment Interactions[J].J .B iolPsychiarry,2000,48 (12):1175-98.
[6]Bale TL,Vale WW.CRF and CRF receptors:Role in stress responsivity and other behaviors[J].Ann Rev Pharmacol Toxicol 2004;44:525-557.
[7]Guillemin R.Hypothalamic hormones a.k.a.hypothalamic releasing factors[J].J Endocrinol.2005 Jan;184(1):11-28.
[8]Chen R,Lewis KA,Perrin MH,Vale WW.Expression cloning of a human corticotropin-releasing-factor receptor[J].Proc Natl Acad Sci USA 1993;90:8967-71.
[9]RivestS,Laflamme N.Neuronal activity and neuropeptide gene Transcription in the brains of immune-challenged rats[J],J Neuroendocrinol,1995;7:501-525.
[10]ImakiT,Nahan JL,Rivier C,Sawehenko PE,Vale W.Differential regulation of CRH mRNA in rat brain regions by glucocorticoids and stress[J].J Neurosci,1991;11:585-599.
[11]Owens MJ,Nemeroff CB.Physiology and Pharmacology of Corticotropin-releasing factor[J].Pharmacol Rev,1991:43:425-473.
[12]Dunn AJ,Berridge CW.Physiological and behavioral responses to Corticotropin-releasing factor administration:is CRF a mediator of anxiety or stress responses ?[J].Brain Rev,1990:15:71-100.
[13]Baigent SM.Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response[J].J .Peptides,2001,22 (5):809-20.
[14]Martins JM,Banks WA,Kastin AJ.Transport of CRH from mouse brain directly affects peripheral production of beta-endorphin by the spleen[J].Am J Physiol 1997;273:E1083-E1089.
[15]Martins JM,Kastin AJ,Banks WA.Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone[J].Neuroendocrinology 1996;63:338-348.
[16]Riviere PJ,Pascaud X,Chevalier E,Junien JL.Fedotozine reversal of peritoneal-irritation-induced ileus in rats:Possible peripheral action on sensory afferents[J].J Pharmacol Exp Ther 1994;270:846-850.
[17]Banks WA and Kastin A J.Passage of peptides across the blood-brain barrier:Pathophysiological perspectives[J].Life Sci 1996;59:1923-1943.
[18]Habib KE et al.Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral,neuroendocrine,and autonomic responses to stress in primates[J].Proc Natl Acad Sci U S A 2000;97:6079-6084.
[19]Gilligan PJ,Robertson DW,Zaczek R.Corticotropin releasing factor (CRF) receptor modulators:progress and opportunities for new therapeutic agents[J].J Med Chem 2000;43:1641-1660.
[20]Kawano H.Daikoku S,Shibasaki T.CRF-containing neurons in the rat Hypothalamus:retrograde tracing and immunohistochemical studies[J].J Comp Neurol,1988;272:260-268.
[21]Lennard DE,Eckert WA,Merehenthalerl.CorticotroPin-releasing hormone neurons in the Parlventricular nucleus Project to the external zzone of the median eminence:a study combining retrograde labeling with immunocytochemistry[J].J Neuroendoerinol,1993;5:175-181.
[22]Rivier C,Vale W.Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo[J].Endocrinology.1983 Sep;l 13(3):939-42.
[23]Brown,M.R,Fisher,L.A,1985.Corticotropin-releasing factor:effects on the autonomic nervous system and visceral systems[J].Fed.Proc.44,243-248.
[24]Nijsen MJ,Croiset G,Stam R,et al .The role of the CRH type 1 receptor in autonomic responses to corticotropin-releasing hormone in the rat[J].J Neuropsychopharmacology,2000,22(4):388-399.
[25]Nakade Y,Yoneda M,Nakamura K,et al .Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats[J].Am J Physiol Regul Integr Comp Physiol.2002 Jun;282(6):R1782-8.
[26]Jezova D,Ochedalski T,Glickman M,et al .Central corticotrophin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress[J].J .Neuroscience,1999,94(3):797-802.
[27]Morimoto A,Nakamori T,Morimoto K,Tan N,Murakami N.The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats[J].J Physiol.1993 Jan;460:221-9.
[28]Shafton AD,Fernley RT,McAllen RM.Is CRF a ganglionic transmitter or modulator in the car sudomotor pathway ?[J].Brain Res,1994,652:129-136.
[29]Song C,Earley B,Leonard BE.Behavioral,neurochemical,and immunological responses to CRF administration.Is CRF a mediator of stress?[J].Ann N Y Acad Sci.1995 Dec 29;771:55-72.
[30]Casadevall M,Saperas E.Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor[J].Am J Phy,276 (4):G1016-1026.
[31]Friedman EM,Irwin MR.A role for CRH and the sympathetic nervous system in stress-induced immunosuppression[J].Ann N Y Acad Sci.1995 Dec 29;771:396-418.
[32]Scha'fer M,Mousa SA,Stein C.Corticotropin-releasing factor in antonociception and inflammation[J].Eur J Pharmacol 323:1-10,1997.
[33]Karalis K,Sano H,Redwine J,Listwak S,Wilder RL,Chrousos GP.Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo[J].Science 254:421-423,1991.
[34]Baigent SM.Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response[J].Peptides.2001 May;22(5):809-20.
[35]Webster EL,Barrientos RM,Contoreggi C,et al.Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced arthritis:role of CRH in peripheral inflammation[J].J Rheumatol,2002,29 (6):1252.
[36]McLoon LK,Sandnas AM,Nockleby KJ,et al.Reduction in vesicant-induced cellular inflammation and hyperalgesia by local inj ection of corticotropin releasing factor in rabbit eyelidf J].Inflamm Res,2002,51 (1):16 -23.
[37]Veraksits A,Bileviciute-Ljungar I,Maaroos J,Vasar E,Lundeberg T.Neuronal mechanisms contribute to corticotropin-releasing factor-induced anti-oedema effect in the rat hind paw[J].Neuropeptides.2000 Apr;34(2):129-34.
[38]Kalantaridou SN,Makrigiannakis A,Zoumakis E,Chrousos GP.Reproductive functions of corticotropin-releasing hormone.Research and potential clinical utility of antalarmins (CRH receptor type 1 antagonists)[J].Am J Reprod Immunol.2004 Apr;51(4):269-74.
[39]Elenkov IJ,Chrousos GP.Stress hormones,Thl /Th2 patterns,pro / anti — inflammatory cytokines and susceptibility to disease[J].Trends Endocrinol Metab,1999,10:359-368.
[40]Angeli A,Masera RG,Sartori ML,Fortunati N,Racca S,Dovio A,Staurenghi A,Frairia R.Modulation by cytokines of glucocorticoid action[J].Ann N Y Acad Sci,1999,876(22):210-220.
[41]Tilders FJ,DeRijk RH,Van Dam AM,et al.Activation of the hypothalamus2p ituitary2adrenal axis by bacterial endotoxins:routes and intermediate signals[J].Psychoneuro—endocrinology,1994,19 (2):209-232.
[42]Wang W,Ji P,Riopelle RJ,et al.Functional expression of corticotropin—releasing hormone (CRH) receptor 1 in cultured rat microglia[J].J Neurochem,2002,80 (2):287-294.
[43]Radulovic M,Spiess J.Immunomodulatory role of the corticotropin-releasing factor[J].J .Arch Immunol Ther Exp,2001,49(1):33-38.
[44]Webster EL,Torpy DJ,Elenkov IJ,et al.Corticotropin-releasing hormone and inflammation[J].Ann N Y Acad Sci,1998,840:21-32.
[45]Baigent SM,Lowry PJ.mRNA expression profiles for corticotrophin-releasing factor (CRF),urocortin,CRF receptors and CRF-binding protein in peripheral rat tissues[J].J Mol Endocrinol.2000 Aug;25(l):43-52.
[46]Jessop DS,Harbuz MS,Lightman SL.CRH in chronic inflammatory stress[J].Peptides.2001 May;22(5):803-7.
[47]Raza J,Massoud AF,Hindmarsh PC,et al .Direct effects of corticotrophin-releasing hormone on stimulated growth hormone secretion[J].J .ClinEndocrinol,1998,48(2):217-222.
[48]Tellam DJ,Mohammad YN,Lovejoy DA.Molecular integration of hypothalamo—pituitary—adrenal axis-related neurohormones on the GnRH neuron[J].Biochem Cell Biol,2000,78 (3):205-216.
[49]Arantxa G,Octavi M.Recovery of the hypothalamic-pituitary-adrenal response to stress[J].J Neuroendocrinology,2000,72:114-125.
[50]Lee S,Kim CK,Rivier C.Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B,corticotropin-releasing factor,corticotropin-releasing factor receptor type 1,and vasopressin in the hypothalamus of the intact rat[J].J Neurosci.1999 Sep l;19(17):7640-7.
[51]Cole RL,Sawchenko PE.Neurotransmitter regulation of cellular activation and neuropeptide gene expression in the paraventricular nucleus of the hypothalamus[J].J Neurosci,2002,22(3):959-969.
[52]McCann SM,Antunes RJ,Franci CR.Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection[J].J .Braz J Med Biol Res,2000,33 (10):1121-1131.
[53]De Kloet ER,Vreugdenhil E,Oitzl MS,Jo?ls M.Brain Corticosteroid Receptor Balance in Health and Disease[J].EndocrRev.1998 Jun;19(3):269-301.
[54]Lovenberg TW,Liaw CW,Grigoriadis DE,et al.Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain[J].Proc Natl Acad Sci U S A 1995;92:836-40.
[55]Chang CP,Pearse RV,O'Connell S,et al.Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain[J].Neuron 1993;11:1187-95.
[56]Chen R,Lewis KA,Perrin MH,et al.Expression cloning of a human corticotropin-releasing-factor receptor[J].Proc Natl Acad Sci U S A 1993;90:8967-71.
[57]Aguilera G,Nikodemova M,Wynn P C,et al.Corticotrop in releasing hormone recep tors:two decades later[J].Peptides,2004,25 (3):319-29.
[58]Smith GW,Aubry JM,Dellu F,et al.Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety,impaired stress response,and aberrant neuroendocrine development[J].Neuron 1998;20:1093-102.
[59]Timpl P,Spanagel R,Sillaber I,et al.Impaired stress response and anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1[J].Nat Genet 1998;19:162-6.
[60]MullerM B,Zimmermann S,Sillaber I,et al.Limbic corticotropin—releasing hormone receptorl mediates anxiety —related behavior and hormonal adap tation to stress[J].N at N eurosci,2003,6(10):1100-7.
[61]Maillot C,Million M,Wei JY,et al.Peripheral corticotropin-releasing factor and stress stimulated colonic motor activity involve type 1 receptor in rats[J].Gastroenterology 2000;119:1569-79.
[62]Tache Y,Martinez V,Wang L,et al.CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscero sensitivity:imp lications for irritable bowel syndrome[J].Br J Pharm acol,2004,141(8):1321-30.
[63]Sagami Y,Shimada Y,Tayama J,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[64]GrammatopoulosD K,Chrousos G P.Functional characteristics of CRH recep tors and potential clinical app lications of CRH2receptor antagonists[J].Trends EndocrinolM etab,2002,13(10):436-44.
[65]Bale T L,Contarino A,Smith GW,et al.Mice deficient for corticotrophin-releasing hormone receptor-2 display anxiety-like behavior and are hypersensitive to stress[J].N at Genet,2000,24(4):410-414.
[66]Coste S C,Kesterson R A,Heldwein KA,et al.Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotrophin releasing hormone receptor-2[J].N at Genet,2000,24 (4):403-9.
[67]Hashimoto K,Makino S,Asaba K,Nishiyama M.Physiological roles of corticotropin-releasing hormone receptor type2[J].Endocr J.2001 Feb;48(l):l-9.
[68]Chen C Y,MillionM,Adelson DW,et al.Intracisternal urocortin inhibits vagally stimulated gastric motility in rats:role of CRF2[J],Br J Pharm acol,2002,136 (2):237-47.
[69]Million M,Wang L,Wang Y,Adelson DW.CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats[J].Gut.2006 Feb;55(2):172-81.Epub 2005 Jun 28.
[70]Herringa RJ,Nanda SA,Hsu DT,Roseboom PH,Kalin NH.The effects of acute stress on the regulation of central and basolateral amygdala CRF-binding protein gene expression[J].Brain Res Mol Brain Res.2004 Nov 24;131(l-2):17-25.
[71]D.P.Behan,E.B.De Souza,P.J.Lowry,E.Potter,P.Sawchenko,W.W.Vale.Corticotropin releasing factor (CRF) binding protein:a novel regulator of CRF and related peptides[J].Front.Neuroendocrinol.16 (1995) 362-382.
[72]Kalin NH,Takahashi LK,Chen FL.Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus[J].Brain Res.1994 Sep 5;656(1):182-6.
[73]Selye H.Syndrome produced by diverse nocuous agents[J].Nature 1936;138:32.
[74]Selye H.A syndrome produced by diverse nocuous agents[J].Nature1936;138:32-36.
[75]Schilling D et al.Low seroprevalence of Helicobacter pylori infection in patients with stress ulcer bleeding-a prospective evaluation of patients on a cardiosurgical intensive care unit[J].Intensive Care Med 2000;26:1832-1836.
[76]Spirt MJ.Stress-related mucosal disease:risk factors and prophylactic therapy[J].Clin Ther.2004Feb;26(2):197-213.
[77]Kawakubo K,Fujishima M.Management of gastrointestinal mucosal damage in patients with cerebrovascular disease[J].Nippon Rinsho.2002 Aug;60(8):1573-9.
[78]Bonaz B.Visceral sensitivity perturbation integration in the brain-gut axis in functional digestive disorders[J].J Physiol Pharmacol.2003 Dec;54 Suppl 4:27-42.
[79]Goyal RK,Hirano I.The enteric nervous system[J].N.Engl.J.Med.1996;334:1106-15.
[80]Wallace J,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,1996May;10(7):731-40.
[81]Kawano S,Tsuji S.Role of mucosal blood flow:a conceptional review in gastric mucosal injury and protection[J].J Gastroenterol Hepatol,2000,15(suppl):1.
[82]Saita H,Murakami M,Kita T.Role of mucosal microcirculation in gastric lesions induced by lateral hypothalamic lesions in rats[J].J Gastroenterol Hepatol.1995 Jul-Aug;10(4):371-8.
[83]段义民、李兆申、湛保先等.内皮素在大鼠冷束缚应激性溃疡中的作用[J].胃肠病学 1998,3(3):178-179.
[84]Kobayashi K,Kashimak K,Higuchi K,et al.The mechanisms of gastrointestinal mucosal injury repair[J].Nippon Rinsho,1998,56(9):2215.
[85]Duerksen DR.Stress-related mucosal disease in critically ill patients[J].Best Pract Res Clin Gastroenterol.2003Jun;17(3):327-44.
[86]Anti M,Armuzzi A,Gasbarrini G.Epithelial cell turnover and apoptosis[J].Ital J Gastroenterol Hepatol,1998,30(Suppl 3):S276-278.
[87]Szabo I,Tarnawski AS.Apoptosis in the gastric mucosa:molecular mechanisms,basic and clinical implications[J].J Physiol Pharmacol,2000,51(1):3.
[88]Konturek PC,Brzozowski T,Konturek SJ et al.Apoptosis in gastric mucosa with stress-induced gastric ulcers[J].J Physiol Pharmacol.1999 Jun;50(2):211-25.
[89]李兆申,刘婧,许国铭等.不同抗溃疡药物对应激性溃疡发生发展过程中细胞凋亡的影响[J].胃肠病学2003,8(1):11-14.
[90]Konturek PC,Brzozowski T,Duda A et al.Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis[J].J Physiol Paris.2001Jan-Dec;95(1-6):361-7.
[91]Kern W,Schiefer B,Schwarzenburg J,et al.Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans[J].Neuroendocrinology,1997,65(4):291-298.
[92]Klamut MJ,Keshavarzian A.Stress ulcer[J].J Assoc Acad Minor Phys.1992;3(3):89-94.
[93]Peterson WL.The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress-related mucosal damage[J].Aliment Pharmacol Ther.1995;9 Suppl 1:43-6.
[94]Datta UK.Effect of heat stress on gastro-intestinal motility in young albino rats[J].Indian J Physiol Pharmacol.2001 Apr;45(2):222-6.
[95]Plourde V.Can J Gastroenterol.Stress-induced changes in the gastrointestinal motor system[J].Can J Gastroenterol.1999 Mar;13 Suppl A:26A-31A.
[96]Thomson AB,Keelan M,Thiesen A,et al.Small bowel review:normal physiology part 2[J].Dig Dis Sci.2001Dec:46(12):2588-2607.
[97]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Pharm Sci Technol Today,1999 Jul,2(7):281-287.
[98]van der Hulst RR,von Meyenfeldt MF,van Kreel BK,et al.Gut permeability,intestinal morphology,and nutritional depletion[J].Nutrition.1998 Jan;14(1):1-6.
[99]MacFie J.Enteral versus parenteral nutrition:the significance of bacterial translocation and gut-barrier function[J].Nutrition,2000 Jul-Aug,16(7-8):606-611.
[100]Saunders PR,Kosecka U,McKay DM,et al.Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine[J].Am J Physiol,1994;267(5Pt1);G794-799.
[101]Santos J,Saperas E,Mourelle M,et al.Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats[J].Gastroenterology,1996:111(6):1465-1473.
[102]Madara JL.Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium:physiological rearrangement of tight junctions[J].J Membr Biol,1990:116(2):177-184.
[103]Kiliaan AJ,Saunders PR,Bijlsma PB et al.Stress stimulates transepithelial macromolecular uptake in rat jejunum[J].Am.J.Physiol.Gastrointest.Liver Physiol.1998;275(5 Part 1):G1037-G1044.
[104]Meddings JB,Swain MG.Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat[J].Gastroenterology,2000;119(4);1019-1028.
[105]黎介寿.肠衰竭-概念、营养支持与肠粘膜屏障维护中国临床营养杂志[J].中国临床营养杂志,2004;3:155-158.
[106]Soderholm JD,Perdue MH.Stress and gastrointestinal tract.Ⅱ.Stress and intestinal barrier function[J].Am J Physiol Gastrointest Liver Physiol,2001;280(1):G7-G13.
[107]Castagliuolo I,Lamont JT,Qiu B,et al.Acute stress causes mucin release from rat colon:role of corticotropin releasing factor and mast cells[J].Am J Physiol,1996:271(5Pt1):G884-892.
[108]Newson B,Dahlstrom A,Enerback L,et al.Suggestive evidence for a direct innervation of mucosal mast cells[J].Neuroscience,1983,10(2):565-570.
[109]Santos J,Yang PC,Soderholm JD,Benjamin M,Perdue MH.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat[J].Gut 2001;48:630-6.
[110]Santos J,Saperas E,Nogueiras C et al.Release of mast cell mediators into the jejunum by cold pain stress in humans[J].Gastroenterology 1998;114:640-8.
[111]Santos J,Benjamin M,Yang PC,et al.Chronic stress impairs rato growth and jejunal epithelial barrier function .role of mast cells[J].Am J Physiol,2000,278:G847-G854.
[112]Wilson LM.Baldwin AL.Environmental stress causes mast cell degranulation,endothelial and epithelial changes,and edema in the rat intestinal mucosa[J].Microcirculation,1999;6(3):189-198.
[113]Castagliuolo I,Wershil BK,Karalis K,et al.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol,1998;274(6Ptl)“.G1094-1100.
[114]Barclay GR,Turnberg LA.Effect of psychological stress on salt and water transport in the human jejunum[J],Gastroenterology,1987;93(1):91-97.
[115]Nakane T,Kanie N,Audhya T,Hollander CS.The effects of centrally administered neuropeptides on the development of gastric lesions in the rat[J].Life Sci 1985;36:1197-1203.
[116]Ray A,Henke PG,Gulati K,Sen P.The amygdaloid complex,corticotrophin releasing factor and stress-induced gastric ulcerogenesis in rats[J].Brain Res 1993;624:286-290.
[117]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,Webster EL,McCann SM,Gold PW.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry.2002;7(5):474-83,433.
[118]Castagliudo I,Leeman SE,Bartolak-Suki E et al.A neurotensin antagonist,SR 48692,inhibits colonic response to immobilization stress in rats[J].Proc.Natl Acad.Sci.USA 1996;93 12 611-15.
[119]Santos J,Saunders PR,Hanssen NP et al.Corticotropin releasing hormone mimics stress induced colonic epithelial pathophysiology in the rat[J].Am.J.Physiol.Gastrointest.Liver Physiol.1999;277 (2 Part 1):G391-G399.
[120]Aird F,Clevenger CV,Prystowsky MB,Redei E.Corticotropinreleasing factor mRNA in rat thymus and spleen[J].Proc Natl Acad Sci USA 1993;90:7104-7108.
[121]Kawahito Y,Sano H,Mukai S,Asai K,Kimura S,Yamamura Y,etal.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut 1995;37:544-551.
[122]Liu S,Gao N,Hu H-Z,Wang X,Wang G-D,Fang X,et al.Distribution and chemical coding of corticotropin-releasing factorimmunoreactive neurons in the guinea pig enteric nervous system[J].J Comp Neurol 2006;494:63-74.
[123]Chatzaki E,Crowe PD,Wang L,Million M,Tache Y,and Grigoriadis DE.CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon[J].J Neurochem 2004;90:309-316.
[124]Kawahito Y,Sano H,Kawata M,Yuri K,Mukai S,Yamamura Y,et al.Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon[J].Gastroenterology 1994;106:859-65.
[125]Bale TL.Sensitivity to stress Dysregulation of CRF pathways and disease development[J].Horm Behav.2005 Jun;48(1):1-10.Epub 2005 Mar 17.
[126]Overton JM,Fisher LA.Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats[J].J Autonom Nerv Syst 35:43-52,1991.
[127]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil 2004;16:137-142.
[128]Santos J,Saunders PR,Hanssen NPM,et al.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[129]Saunders PR,Santos J,Hanssen NP,Yates D,Groot JA,Perdue MH.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci 2002;47:208-215.
[130]Gabry KE,Chrousos GP,Rice KC,Mostafa RM,Sternberg E,Negrao AB,et al.Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs[J].Mol Psychiatry 2002;7:474-483.
[131]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,Bhaskar KR,Nikulasson ST,et al.Acute stress causes mucin release from ratcolon:role of corticotropin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[132]Castagliuolo I,Wershil BK,Karalis K,Pasha A,Nikulasson ST,Bisschops C.Colonic mucin release in response to immobilization stress is mast cell dependent[J].Am J Physiol Gastrointest Liver Physiol 1998;274:G1094-G1100.
[133]V.Martinezl and Y.Tache.CRF1 Receptors as a Therapeutic Target for Irritable Bowel Syndrome[J].Current Pharmaceutical Design,2006,12,4071-4088.
[134]Kawahito Y,Sano H,Mukai S.Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis[J].Gut.1995 Oct;37(4):544-51.
[135]Saunders PR,Santos J,Hanssen NP,et al.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH[J].Dig Dis Sci,2002;47(1):208-215.
[136]Castagliuolo I,Lamont JT,Qiu B,Fleming SM,BhaskarKR,Nikulasson ST,Kornetsky C,and Pothoulakis C.Acute stress causes mucin release from rat colon:role of corticotrophin releasing factor and mast cells[J].Am J Physiol Gastrointest Liver Physiol 1996;271:G884-G892.
[137]Santos J,Saunders PR,Hanssen NP,Yang PC,Yates D,Groot JA,and Perdue MH.Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in therat[J].Am J Physiol Gastrointest Liver Physiol 1999;277:G391-G399.
[138]Million M,Tache?Y,and Anton P.Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis:protective role of brain CRF[J].Am J Physiol Gastrointest Liver Physiol 1999;276:G1027-G1036.
[139]Soderholm JD,Perdue MH.Stress and intestinal barrier function[J].Am.J.Physiol.Gastrointest.Liver Physiol.2001;280:G7-G13.
[140]Tache Y,Martinez V,Million M,and Wang L.Stress and the Gastrointestinal Tract.III.Stress-related alterations of gut motor function:role of brain corticotropin-releasing factor receptors[J].Am J Physiol Gastrointest Liver Physiol 2001;280:G173-G177.
[141]Eutamene H,Theodorou V,Fioramonti J,Bueno L.Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats[J].J Physiol.2003 Dec 15;553(Pt3):959-66.
[142]Ferrier L,Mazelin L,Cenac N,et al.Stress-induced disruption of colonic epithelial barrier:role of interferon-gamma and myosin light chain kinase in mice[J].Gastroenterology 2003;125,795-804.
[143]Barreau F,Carrier C,Leveque M,Ferrier L,Moriez R,Laroute V,Rosztoczy A,Fioramonti J,Bueno L.Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation corticotrophin-releasing factor and nerve growth factor interplay[J].J Physiol.2007 Apr l;580(Pt l):347-56.Epub 2007 Jan 18.
[144]Wallon C,Yang PC,Keita AV,Ericson AC,McKay DM,Sherman PM,Perdue MH,S?derholm JD.Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro[J].Gut.2008 Jan;57(l):50-8.Epub 2007 May 24.
[145]Kokkotou E,Torres D,Moss AC,O'Brien M,Grigoriadis DE,Karalis K,Pothoulakis C.Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses[J].J Immunol.2006 Sep 1;177(5):3355-61.
[146]Martinez V,Wang L,Rivier J,Grigoriadis D,Tache Y.Central CRF,urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice[J].J Physiol.2004 Aprl;556(Pt l):221-34.
[147]Tache Y,Martinez V,Million M,Rivier J.Corticotropin-releasing factor and the brain gut motor response to stress[J].Can.J.Gastroenterol.1999;13 (Suppl.A):18A-25A.
[148]Monnikes H,Tebbe JJ,Hildebrandt M,et al.Role of stress in functional gastrointestinal disorders.Evidence for stress-induced alterations in gastrointestinal motility and sensitivity[J].Dig Dis.2001;19(3):201-11.
[149]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].Neurogastroenterol Motil.2004 Apr;16 Suppl 1:137-42.
[150]Tache Y,Perdue MH.Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function[J].2004;16(suppl 1):137-42.
[151]Lewis MW,Hermann GE,Rogers RC,and Travagli RA.In vitro and in vivo analysis of the effects of corticotropin releasing factor on rat dorsal vagal complex[J].J Physiol 543:135-146,2002.
[152]Tsukamoto K,Nakade Y,Mantyh C,Ludwig K,Pappas TN,and Takahashi T.Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats[J].Am J Physiol Regul Integr Comp Physiol 2006;290:R1537-R1541.
[153]Richard C.Rogers,Gerlinda E.Hermann,and R.Alberto Travagli.Stress and the colon:central-vagal or direct peripheral effect of CRF?[J].Am J Physiol Regul Integr Comp Physiol 2006;290:R1535-R1536.
[154]Sagami Y,Shimada Y,Tayama J,Nomura T,Satake M,Endo Y,et al.Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J].Gut 2004;53:958-64.
[155]Shin Fukudo.Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation[J].J Gastroenterol 2007;42[Suppl ⅩⅦ]:48-51.
[156]Nozu T,Kudaira M.Corticotropin-releasing factor induces rectal hypersensitivity after repetitive painful rectal distention in healthy humans[J].J Gastroenterol.2006 Aug;41(8):740-4.
[157]Greenwood-Van Meerveld B,Johnson AC,Cochrane S,Schulkin J,Myers DA.Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats[J].Neurogastroenterol Motil.2005 Jun;17(3):415-22.
[158]Trimble N,Johnson AC,Foster A,Greenwood-van Meerveld B.Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity[J].Neurogastroenterol Motil.2007 Sep;19(9):754-60.