肠易激综合征肠黏膜SP、SOM、5-HT变化的研究
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摘要
目的:肠易激综合征(Irritable bowel syndrome,IBS)是一种功能性胃肠道疾病。近年来发病率呈逐年增多趋势,严重影响人们生活质量,其发病机制尚不甚清楚。近年来发现肠易激综合征与神经-内分泌-免疫网络失调有关,P物质(substance P,SP)、生长抑素(somatostatin,SOM)、5-羟色胺(5-hydroxytryptamine,5-HT)是该网络的重要因子,是广泛存在于中枢神经系统和肠神经系统(CNS)的神经递质。SP、SOM及5-HT参与了病理和生理状态下的胃肠道运动、感觉和分泌功能的调节,从而使SP、SOM与5-HT成为了人们关注的领域。本实验研究P物质、生长抑素、5-羟色胺在肠易激综合征(IBS)发生、发展中的作用,进一步探讨IBS的发病机理。
方法:选择符合罗马Ⅲ诊断标准的IBS患者59名,按其临床表现分为腹泻组(30例)和便秘组(29例),正常对照者组10名。所有患者结肠镜和病理检查未发现结肠粘膜有炎症和肿瘤等病理改变。取乙状结肠处黏膜组织,进行SP、SOM、5-HT免疫组织化学染色分。观察SP、SOM、5-HT在IBS患者乙状结肠黏膜中的表达情况,并对肠嗜铬细胞(enterochromaffin cell, EC)在乙状结肠的分布数量进行定量分析。实验计量资料数据采用x±S表示,采用SPSS12.0统计软件,选用成组设计的单因素方差分析方法进行统计,检验水准α=0.05;结肠黏膜SP、SOM、5-HT免疫组织化学染色半定量结果,检验方法采用成组设计多个样本比较的秩和检验(Kruskal-Wallis法)及多个样本两两比较的秩和检验(Nemenyi法),检验水准α=0.05。
结果:1 SP的表达主要位于结肠粘膜上皮细胞、肠腺体细胞,粘膜固有层的肥大细胞、中性粒细胞、淋巴细胞及SP免疫阳性纤维等处。SP在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为86.67%(26/30),44.83%(13/29)及90%(9/10)。腹泻型IBS组、便秘型IBS组及对照组患者SP的表达强度差异有非常显著意义(P<0.01);两两比较,便秘型IBS组SP的表达显著低于对照组和腹泻型IBS组,差异有显著意义(P<0.01),而腹泻型IBS患者SP表达与对照组间差别无统计学意义(P>0.05)。
2在消化系统有大量的SOM阳性细胞分布,胃肠道SOM细胞主要分布在粘膜内的δ细胞和粘膜下、麦氏神经内的神经细胞。SOM在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为63.33%(19/30),51.72%(15/29)及60%(6/10)。腹泻型IBS组、便秘型IBS组及对照组患者SOM的表达强度差别无统计学意义(P>0.05)。
3 5-HT在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为90%(27/30),89.66%(26/29)及60%(6/10)。腹泻型IBS组、便秘型IBS组及对照组患者5-HT的表达强度有非常显著差异(P<0.01);对照组的5-HT表达显著低于腹泻型IBS组和便秘型型IBS组,差异有显著意义(P<0.01),IBS患者腹泻组及便秘组的5-HT表达无明显差异(P>0.05)。光镜下正常对照组EC细胞形态多为圆形或椭圆形,体积较小,其颜色基本为淡黄色或棕黄色,极个别为咖啡色。IBS组EC细胞多为锥形或近似菱形,细胞形态饱满,体积较大,其颜色多为咖啡色和黑色。IBS患者组乙状结肠处EC细胞数量较正常对照组显著增加(P<0.05)。IBS患者腹泻组及便秘组EC细胞数量差异无显著性(P>0.05)。
结论:1结肠黏膜中的SP可能对与IBS的发病起着重要的作用。腹泻型IBS组结肠粘膜中SP表达明显增高,提示SP的高表达是引发患者腹痛、大便次数增多、解黏液便的原因之一。
2结肠黏膜中的SOM表达在各组间没有明显差别。IBS患者结肠黏膜SOM表达可能与肠道炎症反应有关。
3 IBS病人结肠黏膜EC细胞数量增加和5-HT分泌增高,可能是产生肠蠕动功能异常或内脏敏感性增加的病理生理基础之一。
Objectives: Irritable bowel syndrome(IBS) which affect the quality of life of people is a functional gastrointestinal tract disease. The incidence of IBS has the increasing trend year after year. Its cause and mechanism remain unclear. It’s thought that IBS is caused by the maladjustment of nerve-internal secretion-immunity network. Substance P(SP)、somatostatin(SOM)and 5-hydroxytryptamine(5-HT)are the important factors in the network and nerve transmitters existing in central nerve system and enteric nervous system (ENS) extensively .SP、SOM and 5-HT play an important role in regulation of gastrointestinal motility, sensation and secretion in pathological and normal stats. SP、SOM and 5-HT have been the new focus studied. So it’s the aim of this research to Study the roles of SP、SOM and 5-HT in the occurrence and the development of irritable bowel syndrome(IBS).
Methods: Of 59 patients with IBS diagnosed by RomeⅢstandard, 30 were enrolled in diarrhoea type group and 29 were enrolled in constipated group. 10 adults without clinical situation were enrolled in control group. There were not pathological changes of colon mucous membranes by colonoscopy and pathology in all patients. Samples from Sigmoid colons mucous membranes fetched by colonscope were prepared for immunocytochemistry in order to observe the expression levels of SP、SOM、5-HT and the number of EC cells in colon mucous membranes of IBS. This experiment’s measure data is expressed by x±S, adopting SPSS 12.0 stat software, choosing two-group one-way ANOVA, test levelα=0.05;As for half quantitative result of SP、SOM、5-HT positive cells immunohistochemistry in colon mucous membranes, two-group multiple-samples rank sum test (Kruskal-Wallis Test) and multiple comparision (Nemenyi Test) was adopted. test levelα=0.05.
Results: 1 SP was mainly expressed in epithelias, intestines gland cells, lymphocytes, mast cells, neutrophil and fibre tissues of colon mucous membranes. SP-positive stain rates were 86.67%(26/30) in D-IBS group,44.83%(13/29) in C-IBS group and 90%(9/10)in control group. There were significant differences of expression of SP among diarrhea-predominant IBS(D-IBS) group, constipated-predominant IBS(C-IBS) group and control group(P<0.01). The expression of SP in C-IBS group was lower than those of the control group and D-IBS group(P<0.01). The expression of SP in D-IBS group were higher than C-IBS group markedly(P < 0.01), but no significances were found in the control group(P>0.05).
2 There have a large number of SOM positive cells in digestive tract. SOM was mainly expressed inδcell and nerve cell of colon mucous membranes. SOM-positive stain rates were 63.33%(19/30) in D-IBS group, 51.72%(15/29) in C-IBS group and 60%(6/10) in control group There were no significant differences of expression intensity of SOM among diarrhea predominant IBS(D-IBS) group, constipated predominant IBS(C-IBS) group and control group(P>0.05).
3 5-HT-positive stain rates were 90%(27/30) in D-IBS group, 89.66%(26/29) in C-IBS group and 60%(6/10) in control group There were significant differences of expression of 5-HT among D-IBS group, C-IBS group and control group(P<0.01). The expression of 5-HT in control group is lower than those of the D-IBS group and C-IBS group(P<0.01). There is no difference of expression of 5-HT between the D-IBS group and C-IBS group (P>0.05). The shape of EC cells is orbicular or elliptical, the volume is little and the colour is mainly pale yellow or buffy in control group and the shape of EC cells is taper or rhombus ,the volume is larger and the colour is coffee or black in IBS groups by light microscopy. The EC cells of sigmoid colon in IBS group is increased remarkably compared with that in control group (P<0.05)。There is no difference of the number of EC cells between the D-IBS group and C-IBS group (P>0.05).
Conclusions: 1 Changes of SP in colonic mucous membranes may play an important role in IBS. Expressions of SP is obviously increased in colon mucous membranes of D-IBS group, which means that the high expressions of SP was involved in one of the reasons why the patients suffer from abdominal pain, increasing of defecation and the mucus stool.
2 There is no difference of expressions of SOM in colon mucous membranes between the control group and IBS group. Expressions of SOM of IBS group may be one reason result in abnormal intestinal inflammatory reaction.
3 The increased number of EC cells and active secretion of 5-HT may be one of reasons resulting in abnormal intestinal peristalsis or increased viscero-sensibility and an important etiological factor of IBS.
方法:选择符合罗马Ⅲ诊断标准的IBS患者59名,按其临床表现分为腹泻组(30例)和便秘组(29例),正常对照者组10名。所有患者结肠镜和病理检查未发现结肠粘膜有炎症和肿瘤等病理改变。取乙状结肠处黏膜组织,进行SP、SOM、5-HT免疫组织化学染色分。观察SP、SOM、5-HT在IBS患者乙状结肠黏膜中的表达情况,并对肠嗜铬细胞(enterochromaffin cell, EC)在乙状结肠的分布数量进行定量分析。实验计量资料数据采用x±S表示,采用SPSS12.0统计软件,选用成组设计的单因素方差分析方法进行统计,检验水准α=0.05;结肠黏膜SP、SOM、5-HT免疫组织化学染色半定量结果,检验方法采用成组设计多个样本比较的秩和检验(Kruskal-Wallis法)及多个样本两两比较的秩和检验(Nemenyi法),检验水准α=0.05。
结果:1 SP的表达主要位于结肠粘膜上皮细胞、肠腺体细胞,粘膜固有层的肥大细胞、中性粒细胞、淋巴细胞及SP免疫阳性纤维等处。SP在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为86.67%(26/30),44.83%(13/29)及90%(9/10)。腹泻型IBS组、便秘型IBS组及对照组患者SP的表达强度差异有非常显著意义(P<0.01);两两比较,便秘型IBS组SP的表达显著低于对照组和腹泻型IBS组,差异有显著意义(P<0.01),而腹泻型IBS患者SP表达与对照组间差别无统计学意义(P>0.05)。
2在消化系统有大量的SOM阳性细胞分布,胃肠道SOM细胞主要分布在粘膜内的δ细胞和粘膜下、麦氏神经内的神经细胞。SOM在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为63.33%(19/30),51.72%(15/29)及60%(6/10)。腹泻型IBS组、便秘型IBS组及对照组患者SOM的表达强度差别无统计学意义(P>0.05)。
3 5-HT在D-IBS组、C-IBS组和正常对照组中的阳性表达率分别为90%(27/30),89.66%(26/29)及60%(6/10)。腹泻型IBS组、便秘型IBS组及对照组患者5-HT的表达强度有非常显著差异(P<0.01);对照组的5-HT表达显著低于腹泻型IBS组和便秘型型IBS组,差异有显著意义(P<0.01),IBS患者腹泻组及便秘组的5-HT表达无明显差异(P>0.05)。光镜下正常对照组EC细胞形态多为圆形或椭圆形,体积较小,其颜色基本为淡黄色或棕黄色,极个别为咖啡色。IBS组EC细胞多为锥形或近似菱形,细胞形态饱满,体积较大,其颜色多为咖啡色和黑色。IBS患者组乙状结肠处EC细胞数量较正常对照组显著增加(P<0.05)。IBS患者腹泻组及便秘组EC细胞数量差异无显著性(P>0.05)。
结论:1结肠黏膜中的SP可能对与IBS的发病起着重要的作用。腹泻型IBS组结肠粘膜中SP表达明显增高,提示SP的高表达是引发患者腹痛、大便次数增多、解黏液便的原因之一。
2结肠黏膜中的SOM表达在各组间没有明显差别。IBS患者结肠黏膜SOM表达可能与肠道炎症反应有关。
3 IBS病人结肠黏膜EC细胞数量增加和5-HT分泌增高,可能是产生肠蠕动功能异常或内脏敏感性增加的病理生理基础之一。
Objectives: Irritable bowel syndrome(IBS) which affect the quality of life of people is a functional gastrointestinal tract disease. The incidence of IBS has the increasing trend year after year. Its cause and mechanism remain unclear. It’s thought that IBS is caused by the maladjustment of nerve-internal secretion-immunity network. Substance P(SP)、somatostatin(SOM)and 5-hydroxytryptamine(5-HT)are the important factors in the network and nerve transmitters existing in central nerve system and enteric nervous system (ENS) extensively .SP、SOM and 5-HT play an important role in regulation of gastrointestinal motility, sensation and secretion in pathological and normal stats. SP、SOM and 5-HT have been the new focus studied. So it’s the aim of this research to Study the roles of SP、SOM and 5-HT in the occurrence and the development of irritable bowel syndrome(IBS).
Methods: Of 59 patients with IBS diagnosed by RomeⅢstandard, 30 were enrolled in diarrhoea type group and 29 were enrolled in constipated group. 10 adults without clinical situation were enrolled in control group. There were not pathological changes of colon mucous membranes by colonoscopy and pathology in all patients. Samples from Sigmoid colons mucous membranes fetched by colonscope were prepared for immunocytochemistry in order to observe the expression levels of SP、SOM、5-HT and the number of EC cells in colon mucous membranes of IBS. This experiment’s measure data is expressed by x±S, adopting SPSS 12.0 stat software, choosing two-group one-way ANOVA, test levelα=0.05;As for half quantitative result of SP、SOM、5-HT positive cells immunohistochemistry in colon mucous membranes, two-group multiple-samples rank sum test (Kruskal-Wallis Test) and multiple comparision (Nemenyi Test) was adopted. test levelα=0.05.
Results: 1 SP was mainly expressed in epithelias, intestines gland cells, lymphocytes, mast cells, neutrophil and fibre tissues of colon mucous membranes. SP-positive stain rates were 86.67%(26/30) in D-IBS group,44.83%(13/29) in C-IBS group and 90%(9/10)in control group. There were significant differences of expression of SP among diarrhea-predominant IBS(D-IBS) group, constipated-predominant IBS(C-IBS) group and control group(P<0.01). The expression of SP in C-IBS group was lower than those of the control group and D-IBS group(P<0.01). The expression of SP in D-IBS group were higher than C-IBS group markedly(P < 0.01), but no significances were found in the control group(P>0.05).
2 There have a large number of SOM positive cells in digestive tract. SOM was mainly expressed inδcell and nerve cell of colon mucous membranes. SOM-positive stain rates were 63.33%(19/30) in D-IBS group, 51.72%(15/29) in C-IBS group and 60%(6/10) in control group There were no significant differences of expression intensity of SOM among diarrhea predominant IBS(D-IBS) group, constipated predominant IBS(C-IBS) group and control group(P>0.05).
3 5-HT-positive stain rates were 90%(27/30) in D-IBS group, 89.66%(26/29) in C-IBS group and 60%(6/10) in control group There were significant differences of expression of 5-HT among D-IBS group, C-IBS group and control group(P<0.01). The expression of 5-HT in control group is lower than those of the D-IBS group and C-IBS group(P<0.01). There is no difference of expression of 5-HT between the D-IBS group and C-IBS group (P>0.05). The shape of EC cells is orbicular or elliptical, the volume is little and the colour is mainly pale yellow or buffy in control group and the shape of EC cells is taper or rhombus ,the volume is larger and the colour is coffee or black in IBS groups by light microscopy. The EC cells of sigmoid colon in IBS group is increased remarkably compared with that in control group (P<0.05)。There is no difference of the number of EC cells between the D-IBS group and C-IBS group (P>0.05).
Conclusions: 1 Changes of SP in colonic mucous membranes may play an important role in IBS. Expressions of SP is obviously increased in colon mucous membranes of D-IBS group, which means that the high expressions of SP was involved in one of the reasons why the patients suffer from abdominal pain, increasing of defecation and the mucus stool.
2 There is no difference of expressions of SOM in colon mucous membranes between the control group and IBS group. Expressions of SOM of IBS group may be one reason result in abnormal intestinal inflammatory reaction.
3 The increased number of EC cells and active secretion of 5-HT may be one of reasons resulting in abnormal intestinal peristalsis or increased viscero-sensibility and an important etiological factor of IBS.
引文
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13 Laforenza U, Cova E, Gastaldi G ,et al. Aquaporin-8 is involved in water transport in isolated superficial colonocytes from rat proximal colon. J Nutr, 2005, 135: 2329-2336
14 Ferri D, Mazzone A,Liquori G, et al. Ontogeny, bistribution and possible functional implications of an unusual aquqporin AQP8 in mouse liver. Hepatology, 2003, 38(4): 947-957
15 Marie-louise E, Lene N, Nejsum V ,et al. Immunolocalization of aquaporin-8 in rat kidney, gastrointestinal tract, testis, and airways. Am J Physiol RenalPhysiol, 2001, 281: F1047–1057
16 Ferri D, Mazzone A, Liquori GE, et al. Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver. Hepatology, 2003, 38: 947-957
17 Yang B, Song Y, Zhao D, et al. Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell, 2005, 288: C1161-1170
18 Hamabate T, Liu C, Takeda Y, et al. Positive and negative regulation of water channel aquaporins in human small intestine by cholera toxin. Microb Pathog, 2002, 32: 273-277
19 Suh HN, Lee SH, Lee MY, et al. High glucose induced translocation of Aquaporin8 to chicken hepatocyte plasma membrane: Involvement of cAMP, PI3K/Akt, PKC, MAPKs, and microtubule. J Cell Biochem, 2007, 18: 188
20 Tsujikawa T, Fukunaga T, Itoh A, et al. Alteration in expression of polyamine and glucose-related enzyme mRNA after small bowel resection in the rat residual ileum. Int J Mol Med, 2002, 10(4): 489-492
21 Fischer H, stenling R, Rubio C, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol, 2001,1:1
22 Hardin JA, Wallace LE, Wong JF, et al. Aquaporin expression is down regulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease andinfectious colitis. Cell Tissue Res, 2004,318: 313-323
23 Yamamoto T, Kuramoto H, Kadowaki M. Down regulation in aquaporin 4 and aquaporin 8 expression of the colon associated with the induction of allergic diarrhea in a mouse model of food allergy. Life Sci. 2007, 81(2): 115-120
24 Zahn A, Moehle C, Langmann T, et al. Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis. World J Gastroenterol. 2007, 13(11): 1687-1695
25 Balboa A, Mearin F. Epidemiological characteristics and socioeconomic importance of irritable bowel syndrome. Rev Esp Enferm Dig 2000, 92: 806-819
26 Nagahama M, Ma N, Semba R, et al. Aquaporin 1 immunoreactive enteric neurons in the rat ileum. Neurosci Lett, 2006, 395: 206-210
27 Van Der Veek PP, Biemond I, Masclee AA. Proximal and distal gut hormone secretion in irritable bowel syndrome. Scand J Gastroenterol, 2006, 41: 170-177
28 王俊平, 侯晓华, 马瑞军. 腹泻型肠易激综合征患者临床特征与结肠黏膜水通道蛋白 8 的表达. 中华内科杂志, 2006, 45: 1000-1003
29 Tamir Gonen, Piotr Sliz, Joerg Kistler, et al. Aquaporin-0 membrane junctions reveal the structure of a closed water pore. NATURE, 2004, 13(429): 193-196
30 Carreras FI, Lehmann GL, Ferri D, et al. Defective hepatocyte aquaporin-8 expression and reduced canalicularmembrane water permeability in estrogen-induced cholestasis. Am J Physiol Gastrointest Liver Physiol. 2007, 292(3): G905-912
31 Carreras FI, Gradilone SA, Mazzone A, et al. Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. Hepatology, 2003, 37: 1026-1033
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1 Benga G, Popescu O, Borza V, et al. Water permeability in human erythrocytes: Identification of membrane proteins in volved in water transport. Eur J Cell Biol, 1986, 41(2): 252-262
2 Benga G. Birth of water channel proteins-the aquaporins. Cell Biol Int, 2003, 27(9): 701-709
3 Agre P, Preston GM, Smith BL, et al. Aquaporin CHIP: the archetypal molecular water channel. Am J Physiol, 1993; 34: F463-476
4 Agre, P, King, L.S. 2002. Aquaporin water channels-from atomic structure to clinical medicine. J Physical. 542: 3-16
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6 Yang B. The human aquaporin gene family(review). Current Genomics, 2000, 1(1): 91-102
7 Verkman AS. Applications of aquaporin inhibitors. DrugNews Perspect, 2003, 14(7): 412-420
8 Verkman AS. Physiological importance of aquaporin water channels. Ann Med, 2002, 34(3): 192-200
9 Bienetr GP, Kristiansen KA, Schulz A, et al. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Boil Chem 2007, 282(2): 1183-1192
10 Calamita G,Mazzone A, Bizzoca A, et al. Expression and immunolocalization of the aquaporin-8 water channel in rat gastrointestinal tract. Eur J Cell Bio, 2001, 80: 711-719
11 Wellner RB, Cotrim AP, Hong S, et al. Localization of AQP5/AQP8 chimeras in MDCK-II cells: exchange of the N- and C-termini. Biochem Biophys Res Commun, 2005, 330(1): 172-177
12 Nagahama M, Ma N, Semba R, et al. Aquaporin 1 immunoreactive enteric nenurons in the rat ileum. Neurosci Lett, 2006, 395: 206-210
13 Laforenza U, Cova E, Gastaldi G ,et al. Aquaporin-8 is involved in water transport in isolated superficial colonocytes from rat proximal colon. J Nutr, 2005, 135: 2329-2336
14 Ferri D, Mazzone A,Liquori G, et al. Ontogeny, bistribution and possible functional implications of an unusual aquqporin AQP8 in mouse liver. Hepatology, 2003, 38(4): 947-957
15 Marie-louise E, Lene N, Nejsum V ,et al. Immunolocalization of aquaporin-8 in rat kidney, gastrointestinal tract, testis, and airways. Am J Physiol RenalPhysiol, 2001, 281: F1047–1057
16 Ferri D, Mazzone A, Liquori GE, et al. Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver. Hepatology, 2003, 38: 947-957
17 Yang B, Song Y, Zhao D, et al. Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell, 2005, 288: C1161-1170
18 Hamabate T, Liu C, Takeda Y, et al. Positive and negative regulation of water channel aquaporins in human small intestine by cholera toxin. Microb Pathog, 2002, 32: 273-277
19 Suh HN, Lee SH, Lee MY, et al. High glucose induced translocation of Aquaporin8 to chicken hepatocyte plasma membrane: Involvement of cAMP, PI3K/Akt, PKC, MAPKs, and microtubule. J Cell Biochem, 2007, 18: 188
20 Tsujikawa T, Fukunaga T, Itoh A, et al. Alteration in expression of polyamine and glucose-related enzyme mRNA after small bowel resection in the rat residual ileum. Int J Mol Med, 2002, 10(4): 489-492
21 Fischer H, stenling R, Rubio C, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol, 2001,1:1
22 Hardin JA, Wallace LE, Wong JF, et al. Aquaporin expression is down regulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease andinfectious colitis. Cell Tissue Res, 2004,318: 313-323
23 Yamamoto T, Kuramoto H, Kadowaki M. Down regulation in aquaporin 4 and aquaporin 8 expression of the colon associated with the induction of allergic diarrhea in a mouse model of food allergy. Life Sci. 2007, 81(2): 115-120
24 Zahn A, Moehle C, Langmann T, et al. Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis. World J Gastroenterol. 2007, 13(11): 1687-1695
25 Balboa A, Mearin F. Epidemiological characteristics and socioeconomic importance of irritable bowel syndrome. Rev Esp Enferm Dig 2000, 92: 806-819
26 Nagahama M, Ma N, Semba R, et al. Aquaporin 1 immunoreactive enteric neurons in the rat ileum. Neurosci Lett, 2006, 395: 206-210
27 Van Der Veek PP, Biemond I, Masclee AA. Proximal and distal gut hormone secretion in irritable bowel syndrome. Scand J Gastroenterol, 2006, 41: 170-177
28 王俊平, 侯晓华, 马瑞军. 腹泻型肠易激综合征患者临床特征与结肠黏膜水通道蛋白 8 的表达. 中华内科杂志, 2006, 45: 1000-1003
29 Tamir Gonen, Piotr Sliz, Joerg Kistler, et al. Aquaporin-0 membrane junctions reveal the structure of a closed water pore. NATURE, 2004, 13(429): 193-196
30 Carreras FI, Lehmann GL, Ferri D, et al. Defective hepatocyte aquaporin-8 expression and reduced canalicularmembrane water permeability in estrogen-induced cholestasis. Am J Physiol Gastrointest Liver Physiol. 2007, 292(3): G905-912
31 Carreras FI, Gradilone SA, Mazzone A, et al. Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. Hepatology, 2003, 37: 1026-1033