目的:检测腹泻型IBS(D-IBS)和便秘型IBS(C-IBS)动物模型肠肌间神经丛的抑制性神经递质一氧化氮(NO)的差异,来探讨肠肌间神经丛神经递质的改变对IBS亚型的影响.方法:采用乙酸灌肠加束缚应激的方法造成D-IBS动物模型,同时设立灌肠对照和...目的:检测腹泻型IBS(D-IBS)和便秘型IBS(C-IBS)动物模型肠肌间神经丛的抑制性神经递质一氧化氮(NO)的差异,来探讨肠肌间神经丛神经递质的改变对IBS亚型的影响.方法:采用乙酸灌肠加束缚应激的方法造成D-IBS动物模型,同时设立灌肠对照和空白对照.采用冰水每日灌胃共14 d的方法造成C-IBS动物模型,同时设立灌胃对照和空白对照.检测各组大鼠粪便性状、内脏敏感性及肠肌间神经丛抑制性神经递质No的含量.结果:在高容量球囊扩张时,D-IBS组大鼠的腹肌收缩次数比C-IBS组及灌肠、空白对照组均明显增多(1.2 mL:7.22±2.01 vs 2.77±0.78,2.89±1.17,3.59±1.08; 1.6 mL:8.11±1.94 vs 2.89±1.67,2.44±1.42, 2.89±1.22,P<0.05).在低容量球囊扩张时,C-IBS组大鼠的腹肌收缩次数比对照组及D-IBS组明显减少(0.4 mL:0.44±0.22 vs 2.44±0.67;0.8 mL:1.56±0.74 vs 6.31±1.74,P<0.05).C-IBS组和灌胃对照组的粪粒数、粪便湿重及粪便含水量均小于空白对照组(2.00±0.66, 2.33±0.50 vs 3.67±1.00;0.80±0.32,1.69±0.49 vs 2.14±0.27;39.24±3.11,40.67±2.84 vs 48.38±2.79, P<0.05);D-IBS组粪便湿重和粪便含水量均高于灌肠和空白对照组(2.31±0.72 vs 1.52±0.58,1.57±0.56, P<0.05;65.31±3.31 vs 53.41±2.73,55.78±3.99. P<0.05).C-IBS组首次排黑便时间比灌胃和空白对照组明显延长(277.89±25.08 vs 205.44±15.74, 189.22±18.45,P<0.05).结肠组织学分析显示各组大鼠均无明显结肠炎性表现.C-IBS组NO阳性的神经元细胞数显著多于D-IBS组和对照组(303.50±14.43 vs 200.89±16.67,185.78±16.66,P<0.01),而D-IBS组和对照组NO阳性的神经元细胞数无显著差异(P>0.05).结论:抑制性神经递质NO的数量的增加与IBS不同亚型、内脏敏感性及动力异常相关,提示NO的改变与 IBS不同亚型发病机制有一定关系.展开更多
Objective:To investigate the changes of intestinal mucosa tight junctions (TJs) claudin-1, -3,-4 proteins and mRNA changes in patients with irritable bowel syndrome (IBS) and to elucidate their possible roles in the c...Objective:To investigate the changes of intestinal mucosa tight junctions (TJs) claudin-1, -3,-4 proteins and mRNA changes in patients with irritable bowel syndrome (IBS) and to elucidate their possible roles in the changes of bowel evacuation habit and formation.Methods:Claudin-1,-3,-4 proteins and mRNA were evaluated in intestinal mucosa in control group,D-IBS (diarrhea IBS) group and C-IBS (constipation IBS) group with immunohistochemical assay and Realtime-PCR.Results:It was observed that claudin-1,-3,-4 proteins were localized in the membranes of epithelial cells along the entire length of the plasma membrane including the apical end of the epithelial cells.The claudins were concentrated at the site of TJs only.Claudin-1,-3,-4 mRNA and claudin-1 protein in small intestinal mucosa and colonal mu- cous in D-IBS group were significantly downregulated (P<0.05).Claudin-1,-3,-4 mRNA and proteins in small intestinal mucosa and colonal mucous in C-IBS group were significantly upregulated (P<0.05). There was no significant difference in the expression of claudin-3 protein in both small intestinal mucosa and colonal mucous between D-IBS group and control group(P>0.05).Similarly,no significantly differ- ent expression of claudin-4 protein in colonal mucous in D-IBS group was found compared with control group (P>0.05).Otherwise,the expression of claudin-4 protein in small intestinal mucosa decreased in D-IBS group (P<0.05).Conclusion:Claudin-1,-3,-4 may play a potential important role in the changes of bowel evacuation habit and formation in patients with IBS.It is not due to the localization changes of claudin proteins in T J,but may be caused by the quantitative changes of the expression of TJ proteins and mRNA.展开更多
文摘目的:检测腹泻型IBS(D-IBS)和便秘型IBS(C-IBS)动物模型肠肌间神经丛的抑制性神经递质一氧化氮(NO)的差异,来探讨肠肌间神经丛神经递质的改变对IBS亚型的影响.方法:采用乙酸灌肠加束缚应激的方法造成D-IBS动物模型,同时设立灌肠对照和空白对照.采用冰水每日灌胃共14 d的方法造成C-IBS动物模型,同时设立灌胃对照和空白对照.检测各组大鼠粪便性状、内脏敏感性及肠肌间神经丛抑制性神经递质No的含量.结果:在高容量球囊扩张时,D-IBS组大鼠的腹肌收缩次数比C-IBS组及灌肠、空白对照组均明显增多(1.2 mL:7.22±2.01 vs 2.77±0.78,2.89±1.17,3.59±1.08; 1.6 mL:8.11±1.94 vs 2.89±1.67,2.44±1.42, 2.89±1.22,P<0.05).在低容量球囊扩张时,C-IBS组大鼠的腹肌收缩次数比对照组及D-IBS组明显减少(0.4 mL:0.44±0.22 vs 2.44±0.67;0.8 mL:1.56±0.74 vs 6.31±1.74,P<0.05).C-IBS组和灌胃对照组的粪粒数、粪便湿重及粪便含水量均小于空白对照组(2.00±0.66, 2.33±0.50 vs 3.67±1.00;0.80±0.32,1.69±0.49 vs 2.14±0.27;39.24±3.11,40.67±2.84 vs 48.38±2.79, P<0.05);D-IBS组粪便湿重和粪便含水量均高于灌肠和空白对照组(2.31±0.72 vs 1.52±0.58,1.57±0.56, P<0.05;65.31±3.31 vs 53.41±2.73,55.78±3.99. P<0.05).C-IBS组首次排黑便时间比灌胃和空白对照组明显延长(277.89±25.08 vs 205.44±15.74, 189.22±18.45,P<0.05).结肠组织学分析显示各组大鼠均无明显结肠炎性表现.C-IBS组NO阳性的神经元细胞数显著多于D-IBS组和对照组(303.50±14.43 vs 200.89±16.67,185.78±16.66,P<0.01),而D-IBS组和对照组NO阳性的神经元细胞数无显著差异(P>0.05).结论:抑制性神经递质NO的数量的增加与IBS不同亚型、内脏敏感性及动力异常相关,提示NO的改变与 IBS不同亚型发病机制有一定关系.
基金Supported by the National Natural Science Foundation of China(No.30170414)
文摘Objective:To investigate the changes of intestinal mucosa tight junctions (TJs) claudin-1, -3,-4 proteins and mRNA changes in patients with irritable bowel syndrome (IBS) and to elucidate their possible roles in the changes of bowel evacuation habit and formation.Methods:Claudin-1,-3,-4 proteins and mRNA were evaluated in intestinal mucosa in control group,D-IBS (diarrhea IBS) group and C-IBS (constipation IBS) group with immunohistochemical assay and Realtime-PCR.Results:It was observed that claudin-1,-3,-4 proteins were localized in the membranes of epithelial cells along the entire length of the plasma membrane including the apical end of the epithelial cells.The claudins were concentrated at the site of TJs only.Claudin-1,-3,-4 mRNA and claudin-1 protein in small intestinal mucosa and colonal mu- cous in D-IBS group were significantly downregulated (P<0.05).Claudin-1,-3,-4 mRNA and proteins in small intestinal mucosa and colonal mucous in C-IBS group were significantly upregulated (P<0.05). There was no significant difference in the expression of claudin-3 protein in both small intestinal mucosa and colonal mucous between D-IBS group and control group(P>0.05).Similarly,no significantly differ- ent expression of claudin-4 protein in colonal mucous in D-IBS group was found compared with control group (P>0.05).Otherwise,the expression of claudin-4 protein in small intestinal mucosa decreased in D-IBS group (P<0.05).Conclusion:Claudin-1,-3,-4 may play a potential important role in the changes of bowel evacuation habit and formation in patients with IBS.It is not due to the localization changes of claudin proteins in T J,but may be caused by the quantitative changes of the expression of TJ proteins and mRNA.