丁酸钠灌肠对大鼠结肠直肠感觉的影响
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摘要
【目的】了解丁酸钠灌肠对大鼠内脏感觉功能的影响;探讨食物纤维对内脏感觉功能的影响。
【方法】将16只Sprague-Dawley大鼠随机分为对照组和实验组,将丁酸钠配成200ml/L的溶液,并调节pH至中性(pH6.9)。实验组大鼠采用丁酸钠溶液灌肠。经肛门插入导管至距肛门7cm,注入1ml丁酸钠溶液,每天2次,连续3天。同时对照组大鼠给予生理盐水灌肠,每天2次,连续3天。两组大鼠均在第一次灌肠后的第3,6,9,12,15,18天行结直肠气囊扩张(colorectal distension,CRD),观察大鼠的腹壁回撤反射(abdominal with drawl relex,AWR),以测定内脏感觉功能。试验结束后处死大鼠,取出直肠,进行肉眼观评分及组织学炎症细胞计数。
【结果】在第3,6,9,12天,在20,40,60,80mmHg的扩张压力下,实验组的AWR评分明显高于对照组(P<0.05);而在第15,18天,在20,40,60,80mmHg的扩张压力下,实验组的AWR评分与对照组无显著差异(P>0.05)。大鼠结肠粘膜的肉眼观及组织学改变在实验组和对照组比较无显著差异。
【结论】丁酸钠溶液反复灌肠在大鼠可导致内脏感觉过敏,且在结肠粘膜不造成炎症,故可以这一非炎性慢性结肠感觉过敏模型作为研究IBS的又一新有用的研究工具。
【Objective】To research the influence of sodium butyrate on visceral sensation of rat splanchnesthesia by coloclysis, and investigate the influence dietary fiber has on visceral sensation.
【Methods】16 SD-rats were divided into control group and experiment group with 8 rats in each group. sodium butyrate solution(200mmol/L,pH 6.9) was made previously. Control group and experiment group were dealed with saline solution and sodium butyrate solution respectively. Each group was dealed with the corresponding solution in perstetur 3 days(two times each day, 1Ml solution each time). Abdominal withdrawl(AWR) after colorectal distension(CRD) was observed in 3th, 6th, 9th, 12th, 15th and 18th day respectively. Rats were killede and the rectum was observed by gross appearance and cell counting of histology at the end of experiment.
【Results】Under the colorectal distension(20, 40, 60 and 80mmHg respectively) AWR mark of experiment group was obvious higher than that of control group in 3th, 6th, 9th and 12th day(P>0.05), but no obvious difference in 15th and 18th day(P>0.05).
【Conclusion】Repetatur usage of sodium butyrate solution may cause visceral hyperaesthesia without inflammation on mucous membrane of colon. These results present our noninflammatory model of chronic colonic hypersensitivity as a useful novel tool for studying IBS. By the methods of gross appearance and cell counting of histology, there was no significant deviation between two groups.
【方法】将16只Sprague-Dawley大鼠随机分为对照组和实验组,将丁酸钠配成200ml/L的溶液,并调节pH至中性(pH6.9)。实验组大鼠采用丁酸钠溶液灌肠。经肛门插入导管至距肛门7cm,注入1ml丁酸钠溶液,每天2次,连续3天。同时对照组大鼠给予生理盐水灌肠,每天2次,连续3天。两组大鼠均在第一次灌肠后的第3,6,9,12,15,18天行结直肠气囊扩张(colorectal distension,CRD),观察大鼠的腹壁回撤反射(abdominal with drawl relex,AWR),以测定内脏感觉功能。试验结束后处死大鼠,取出直肠,进行肉眼观评分及组织学炎症细胞计数。
【结果】在第3,6,9,12天,在20,40,60,80mmHg的扩张压力下,实验组的AWR评分明显高于对照组(P<0.05);而在第15,18天,在20,40,60,80mmHg的扩张压力下,实验组的AWR评分与对照组无显著差异(P>0.05)。大鼠结肠粘膜的肉眼观及组织学改变在实验组和对照组比较无显著差异。
【结论】丁酸钠溶液反复灌肠在大鼠可导致内脏感觉过敏,且在结肠粘膜不造成炎症,故可以这一非炎性慢性结肠感觉过敏模型作为研究IBS的又一新有用的研究工具。
【Objective】To research the influence of sodium butyrate on visceral sensation of rat splanchnesthesia by coloclysis, and investigate the influence dietary fiber has on visceral sensation.
【Methods】16 SD-rats were divided into control group and experiment group with 8 rats in each group. sodium butyrate solution(200mmol/L,pH 6.9) was made previously. Control group and experiment group were dealed with saline solution and sodium butyrate solution respectively. Each group was dealed with the corresponding solution in perstetur 3 days(two times each day, 1Ml solution each time). Abdominal withdrawl(AWR) after colorectal distension(CRD) was observed in 3th, 6th, 9th, 12th, 15th and 18th day respectively. Rats were killede and the rectum was observed by gross appearance and cell counting of histology at the end of experiment.
【Results】Under the colorectal distension(20, 40, 60 and 80mmHg respectively) AWR mark of experiment group was obvious higher than that of control group in 3th, 6th, 9th and 12th day(P>0.05), but no obvious difference in 15th and 18th day(P>0.05).
【Conclusion】Repetatur usage of sodium butyrate solution may cause visceral hyperaesthesia without inflammation on mucous membrane of colon. These results present our noninflammatory model of chronic colonic hypersensitivity as a useful novel tool for studying IBS. By the methods of gross appearance and cell counting of histology, there was no significant deviation between two groups.
引文
[1]Mayer EA, Collins SM. Evolving pathophysiologic models of functional gastrointestinal disorders. Gastroenterology,2002,122:2032-2048.
[2]李俊霞,刘新光,谢鹏雁,等.钙离子在大鼠结肠平滑肌运动中作用机制的研究.中华内科杂志, 2000,39:588-591.
[3] BourduS,Dapoigny M, Chapuy E, Artigue F, Vasson MP,Dechelotte P, Bommelaer G, Eschalier A, Ardid D. Rectal instillation of butyrate provides a novel clinically relevant model of noninflammatory colonic hypersensitivity in rats. Gastroenterology. 2005 Jun;128(7):1996-2008.
[4] Liang LX, Zhang Q, Hou XH. Antinociceptive property of tagaserod in a rat model of chronic visceral hypersensitivity. Chin J Dig Dis , 2005, 6:21-25.
[5]Al Chaer ED, Kawasaki M, Pasricha PJ.A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 2000;119(5):1276-1285.
[6]Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795-803.
[7]Dolhart RE , Dentler M , Barrow LL. The effect of various types of therapy in the management of the irritable bowel syndrome. Illinois Med J , 1946 ,90 :2872289.
[8] Mertz H. Review article :visceral hypersensitivity. Aliment Pharmacol Ther, 2003,17: 623-633.
[9]王伟岸,钱家鸣.肠易激综合征的发病机制[ J ].胃肠病学和肝病学杂志,2001, 10 (2):103
[10] Yadid G, Nakash R , Deri I , et al. Elucidation of the neurobiology of depression : insights from a novel genetic animal model. Prog Neurobiol , 2000 ,62 :353-378.
[11]Read NW, Al Janabi MN, Bates TE, Holgate AM, Cann PA, Kinsman RI, McFarlane A, Brown C. Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.Gut 1985;26:834-842.
[12]Read NW, Al Janabi MN, Bates TE, Holgate AM, Cann PA, Kinsman RI, McFarlane A,Brown C. Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.Gut 1985;26:834-842.
[13]Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowelsyndrome.Gastroenterology 2002;123:2108-2131.
[14]Delvaux M.Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome.Gut 2002;51:167-171.
[15]MertzH,NaliboffB,MunakataJ,etal.Alter edr ectal perception is a biological marker of patienswith irritable bowel syndrome.Gastroenterology,1995,109(1):40-52
[16]Bueno L,Fioramonti J,Delvaux M,etal. Mediators and pharmacology of visceral sensitivity:from basic to clinical investigations. Gastroenterology,1997,112:1714-1743.
[17]Al - chaer ED, Kawasaki M, Pasricha PJ. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development . Gastroenterology ,2000,119:1276-1285.
[18]王伟岸,钱家鸣,潘国宗.肠易激综合征的发病机制.胃肠病学和肝病学杂志,2001,10:99-102.
[19]Naliboff BD,Chang L, Munakata J,et al.Towards an integrative model of irritable bowel syndrome. Prog Brain Res , 2000 , 122 :413-423.
[20]Tarrerias AL, Millecamps M, Alloui A, Beaughard C, Kemeny JL, Bourdu S, Bommelaer G, Eschalier A, Dapoigny M, Ardid D. Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Pain 2002;100:91-97.
[21]Glansen M R , Mortensen P B. Kinetic studies on the metabolism of short chain fatty acids and glucose in isolated rat colonocytes. Gastroentology ,1994 ,5 :423～432
[22]Heaton KW. Effect of diet on intestinal function and dysfunction. In Pathogenesis of functional bowel disease, eds W.J. Snape Jr. New York, NY: Plenum; 1989. p.79-100.
[23]Treem WR, Ahsan N, Kastoff G, Hyams JS. Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr 1996;23:280-286.
[24]Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet 1994;344:39-40.
[1] Dolhart RE , Dentler M , Barrow LL. The effect of various types of therapy in the management of the irritable bowel syndrome. Illinois Med J , 1946 ,90 :287-289.
[2] DOUGLAS A. DROSSMAN, Guest Editor The Functional Gastrointestinal Disorders and the Rome III Process. GASTROENTEROLOGY 2006;130:1377–1390
[3] Mayer EA, Collins SM. Evolving pathophysiologic models of functional gastrointestinal disorders [J] .Gastroenterology, 2002,122;2032-2048.
[4]侯晓华.功能性胃肠疾病与内脏感觉过敏[J].基础医学与临床,2003,23 ( Zl) :6-7.
[5]赵晓志,王邦茂,杨玉龙,等.肠易激综合症患者在直肠冷/热刺激扩张试验中的感觉变化探讨[J].基础医学与临床,2003,23 ( Zl) :84-85
[6]王伟岸,钱家鸣,潘国宗.肠易激综合征的发病机制.胃肠病学和肝病学杂志,2001 ,10 :99-102.
[7] Yadid G, Nakash R,Deri I, etal. Elucidation of the neurobiology of depression : insights from a novel genetic animal model. Prog Neurobiol , 2000 ,62 :353-378.
[8] Williams CL,Villar RG,Peterson JM,etal.Stress-induced changes in intestinal transit in he rat : a model for irritable bowel syndrome. Gastroenterology,1988 ,94(3):611-621.
[9] Mayer EA , Naliboff BD,Chang L , et al. Gastrointest liver physiol V. Stress and irritable bowel syndrome. AmJ Physiol , 2001 ,280 :G519-G524.
[10] Mayer EA. Emerging disease model for functional gastrointestinal disorders. Am J Med,1999,107(5A):12S-19S.
[11] Naliboff BD , Chang L ,Munakata J,etal.Towards an integrative model of irritable bowel syndrome. Prog Brain Res,2000,122:413-423.
[12] Mayer EA,Collins SM.Evolving pathophysiologic models of functional gastrointestinal disorders. Gastroenterology ,2002 ,122 :2032-2048.
[13]李俊霞,刘新光,谢鹏雁,等.钙离子在大鼠结肠平滑肌运动中作用机制的研究.中华内科杂志, 2000 ,39 :588-591.
[14] Posscrud I , Agerforz P , Ekman R , eta1 . Altered viscera perceptual and neu—roendocrine response in patients with irritable bowel syndrome duringmentalstress.Gut.2004,53(8):1102.1108.
[15] BRADESI S,EUTAMENE,H.GARCIA-VILLAR R,eta1.Acute andchronk atress differently afect visceral sensitivity to rectal distension in female rats.Nrurogastroentero[Modl,2002,l4(I):75-82.
[16] GueM ,Ri o-LachezeC D,Eu tameneH ,etal .Str essin ducedv isceralhy persensitivity to rectal distension in rats:role of CRF and inast cells.Neurogastroen ter ol M oti1,1997,9:271-279.
[17] Al-ChaerE D,Ka wasakiM ,Pa srichaP J.A newm odelo fc hronic hypersensitivity in adult rats induced by colon initation during posm visceralatal development. Gastroenterology,2000,119:1276-1285
[18]孙燕,柳锋霖,钱伟等.急性和慢性束缚应激对大鼠内脏敏感性的影响.胃肠病学和肝病学杂志2005,l4:634-636
[19]王伟岸,钱家鸣,潘国宗,等.脑一肠互动指向性条件应激肠易激综合征动物模型的建立[J].中华消化杂志,2004 ,24;590-593.
[20] Coutinho S, Plotsky PM, Sablad M,etal. Neonatal maternal separationa lterss tress-inducedr esponset ov iscerosomat ic n oc iceptivest imuliin r ats[J ] . AmJ PhysiolG strointest Liver Physiol,20 02,282:3 07-316
[21]刘清华.肠易激综合征动物模型复制思路及方法[J].国外医学(消化系疾病分册),2002,22 :154-156.
[22]刘新光.模拟肠易激综合征动物模型研究的评述[J].胃肠病学和肝病学杂志,2004;12;329-330.
[23]彭丽华,杨云生,孙刚,等.便秘型肠易激综合征新概念模型的建立[J].世界华人消化杂志,2004,12:112 -116 . [24」Collins SM, Mchugh K, Jacobson K, et al. Previous inflame Mation alters the response of the rat colont os tress[J] .Gastroenterology,1996,111:1509-1515.
[25] L aJH ,K imT W,Su ngT S,et al .V isceralhy persensitivity and a lte red colonicm otilitya fters ubsidence of inflammation in a rat model of colitis[J ] .WorlJ G astroenterol,2003 ,9 ;2791-2795.
[26] Chen JJ, Li Z, Pan H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-afinity serotonin transporter:abnormal intestinal motility and the expression of cation transporters[J ] . JN eurosci,2001,21:6348一6361.
[2]李俊霞,刘新光,谢鹏雁,等.钙离子在大鼠结肠平滑肌运动中作用机制的研究.中华内科杂志, 2000,39:588-591.
[3] BourduS,Dapoigny M, Chapuy E, Artigue F, Vasson MP,Dechelotte P, Bommelaer G, Eschalier A, Ardid D. Rectal instillation of butyrate provides a novel clinically relevant model of noninflammatory colonic hypersensitivity in rats. Gastroenterology. 2005 Jun;128(7):1996-2008.
[4] Liang LX, Zhang Q, Hou XH. Antinociceptive property of tagaserod in a rat model of chronic visceral hypersensitivity. Chin J Dig Dis , 2005, 6:21-25.
[5]Al Chaer ED, Kawasaki M, Pasricha PJ.A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 2000;119(5):1276-1285.
[6]Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795-803.
[7]Dolhart RE , Dentler M , Barrow LL. The effect of various types of therapy in the management of the irritable bowel syndrome. Illinois Med J , 1946 ,90 :2872289.
[8] Mertz H. Review article :visceral hypersensitivity. Aliment Pharmacol Ther, 2003,17: 623-633.
[9]王伟岸,钱家鸣.肠易激综合征的发病机制[ J ].胃肠病学和肝病学杂志,2001, 10 (2):103
[10] Yadid G, Nakash R , Deri I , et al. Elucidation of the neurobiology of depression : insights from a novel genetic animal model. Prog Neurobiol , 2000 ,62 :353-378.
[11]Read NW, Al Janabi MN, Bates TE, Holgate AM, Cann PA, Kinsman RI, McFarlane A, Brown C. Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.Gut 1985;26:834-842.
[12]Read NW, Al Janabi MN, Bates TE, Holgate AM, Cann PA, Kinsman RI, McFarlane A,Brown C. Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.Gut 1985;26:834-842.
[13]Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowelsyndrome.Gastroenterology 2002;123:2108-2131.
[14]Delvaux M.Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome.Gut 2002;51:167-171.
[15]MertzH,NaliboffB,MunakataJ,etal.Alter edr ectal perception is a biological marker of patienswith irritable bowel syndrome.Gastroenterology,1995,109(1):40-52
[16]Bueno L,Fioramonti J,Delvaux M,etal. Mediators and pharmacology of visceral sensitivity:from basic to clinical investigations. Gastroenterology,1997,112:1714-1743.
[17]Al - chaer ED, Kawasaki M, Pasricha PJ. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development . Gastroenterology ,2000,119:1276-1285.
[18]王伟岸,钱家鸣,潘国宗.肠易激综合征的发病机制.胃肠病学和肝病学杂志,2001,10:99-102.
[19]Naliboff BD,Chang L, Munakata J,et al.Towards an integrative model of irritable bowel syndrome. Prog Brain Res , 2000 , 122 :413-423.
[20]Tarrerias AL, Millecamps M, Alloui A, Beaughard C, Kemeny JL, Bourdu S, Bommelaer G, Eschalier A, Dapoigny M, Ardid D. Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Pain 2002;100:91-97.
[21]Glansen M R , Mortensen P B. Kinetic studies on the metabolism of short chain fatty acids and glucose in isolated rat colonocytes. Gastroentology ,1994 ,5 :423～432
[22]Heaton KW. Effect of diet on intestinal function and dysfunction. In Pathogenesis of functional bowel disease, eds W.J. Snape Jr. New York, NY: Plenum; 1989. p.79-100.
[23]Treem WR, Ahsan N, Kastoff G, Hyams JS. Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr 1996;23:280-286.
[24]Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet 1994;344:39-40.
[1] Dolhart RE , Dentler M , Barrow LL. The effect of various types of therapy in the management of the irritable bowel syndrome. Illinois Med J , 1946 ,90 :287-289.
[2] DOUGLAS A. DROSSMAN, Guest Editor The Functional Gastrointestinal Disorders and the Rome III Process. GASTROENTEROLOGY 2006;130:1377–1390
[3] Mayer EA, Collins SM. Evolving pathophysiologic models of functional gastrointestinal disorders [J] .Gastroenterology, 2002,122;2032-2048.
[4]侯晓华.功能性胃肠疾病与内脏感觉过敏[J].基础医学与临床,2003,23 ( Zl) :6-7.
[5]赵晓志,王邦茂,杨玉龙,等.肠易激综合症患者在直肠冷/热刺激扩张试验中的感觉变化探讨[J].基础医学与临床,2003,23 ( Zl) :84-85
[6]王伟岸,钱家鸣,潘国宗.肠易激综合征的发病机制.胃肠病学和肝病学杂志,2001 ,10 :99-102.
[7] Yadid G, Nakash R,Deri I, etal. Elucidation of the neurobiology of depression : insights from a novel genetic animal model. Prog Neurobiol , 2000 ,62 :353-378.
[8] Williams CL,Villar RG,Peterson JM,etal.Stress-induced changes in intestinal transit in he rat : a model for irritable bowel syndrome. Gastroenterology,1988 ,94(3):611-621.
[9] Mayer EA , Naliboff BD,Chang L , et al. Gastrointest liver physiol V. Stress and irritable bowel syndrome. AmJ Physiol , 2001 ,280 :G519-G524.
[10] Mayer EA. Emerging disease model for functional gastrointestinal disorders. Am J Med,1999,107(5A):12S-19S.
[11] Naliboff BD , Chang L ,Munakata J,etal.Towards an integrative model of irritable bowel syndrome. Prog Brain Res,2000,122:413-423.
[12] Mayer EA,Collins SM.Evolving pathophysiologic models of functional gastrointestinal disorders. Gastroenterology ,2002 ,122 :2032-2048.
[13]李俊霞,刘新光,谢鹏雁,等.钙离子在大鼠结肠平滑肌运动中作用机制的研究.中华内科杂志, 2000 ,39 :588-591.
[14] Posscrud I , Agerforz P , Ekman R , eta1 . Altered viscera perceptual and neu—roendocrine response in patients with irritable bowel syndrome duringmentalstress.Gut.2004,53(8):1102.1108.
[15] BRADESI S,EUTAMENE,H.GARCIA-VILLAR R,eta1.Acute andchronk atress differently afect visceral sensitivity to rectal distension in female rats.Nrurogastroentero[Modl,2002,l4(I):75-82.
[16] GueM ,Ri o-LachezeC D,Eu tameneH ,etal .Str essin ducedv isceralhy persensitivity to rectal distension in rats:role of CRF and inast cells.Neurogastroen ter ol M oti1,1997,9:271-279.
[17] Al-ChaerE D,Ka wasakiM ,Pa srichaP J.A newm odelo fc hronic hypersensitivity in adult rats induced by colon initation during posm visceralatal development. Gastroenterology,2000,119:1276-1285
[18]孙燕,柳锋霖,钱伟等.急性和慢性束缚应激对大鼠内脏敏感性的影响.胃肠病学和肝病学杂志2005,l4:634-636
[19]王伟岸,钱家鸣,潘国宗,等.脑一肠互动指向性条件应激肠易激综合征动物模型的建立[J].中华消化杂志,2004 ,24;590-593.
[20] Coutinho S, Plotsky PM, Sablad M,etal. Neonatal maternal separationa lterss tress-inducedr esponset ov iscerosomat ic n oc iceptivest imuliin r ats[J ] . AmJ PhysiolG strointest Liver Physiol,20 02,282:3 07-316
[21]刘清华.肠易激综合征动物模型复制思路及方法[J].国外医学(消化系疾病分册),2002,22 :154-156.
[22]刘新光.模拟肠易激综合征动物模型研究的评述[J].胃肠病学和肝病学杂志,2004;12;329-330.
[23]彭丽华,杨云生,孙刚,等.便秘型肠易激综合征新概念模型的建立[J].世界华人消化杂志,2004,12:112 -116 . [24」Collins SM, Mchugh K, Jacobson K, et al. Previous inflame Mation alters the response of the rat colont os tress[J] .Gastroenterology,1996,111:1509-1515.
[25] L aJH ,K imT W,Su ngT S,et al .V isceralhy persensitivity and a lte red colonicm otilitya fters ubsidence of inflammation in a rat model of colitis[J ] .WorlJ G astroenterol,2003 ,9 ;2791-2795.
[26] Chen JJ, Li Z, Pan H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-afinity serotonin transporter:abnormal intestinal motility and the expression of cation transporters[J ] . JN eurosci,2001,21:6348一6361.
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