机构地区:[1]南京医科大学第一附属医院消化内科,210029
出 处:《胃肠病学》2006年第8期462-467,共6页Chinese Journal of Gastroenterology
基 金:江苏省"135工程"重点人才基金项目(No.RC2003087);江苏省自然科学基金项目(No.BK2004158)资助
摘 要:背景:慢传输型便秘的发病机制尚不清楚。近年Cajal间质细胞(interstitialcellsofCajal,ICC)对胃肠平滑肌的起搏作用和介导神经递质的作用已被人们所认识,且在一些胃肠动力障碍性疾病中存在ICC数量和结构的异常改变。目的:探讨ICC在慢传输运动小鼠结肠组织中的改变。方法:经吗啡诱导建立结肠慢传输运动小鼠模型,采用免疫组化法观察各组小鼠结肠组织ICC的表达和分布;采用Westernblot蛋白印迹试验和逆转录聚合酶链反应(RT-PCR)分析各组小鼠结肠组织c-Kit蛋白和c-kitmRNA的表达。结果:①45天后两实验组小鼠近端结肠组织免疫组化c-kit阳性细胞较对照组显著减少(P<0.01),实验组Ⅱ较实验组Ⅰc-kit阳性细胞减少更明显(P<0.01);60天后停吗啡组的c-kit阳性细胞较纳洛酮阻断组和对照组显著减少(P<0.01)。小鼠远端结肠组织c-kit阳性细胞在所有组别之间无显著差异。②45天后两实验组小鼠近端结肠组织c-Kit蛋白和c-kitmRNA的表达较对照组均显著减少(P均<0.01);60天后停吗啡组近端结肠组织c-Kit蛋白和c-kitmRNA的表达仍较纳洛酮阻断组和对照组显著减少(P<0.05和P<0.01)。结论:吗啡诱导的慢传输运动小鼠近端结肠组织中ICC数量下降,c-Kit蛋白和c-kitmRNA的表达明显减少,提示近端结肠ICC减少可能是结肠慢传输运动的原因之一;停用吗啡未能逆转ICC的变化,结肠慢传输运动也无改善。纳洛酮阻断后,ICC的变化基本恢复,结肠动力改善,纳洛酮可能阻止和恢复吗啡诱导的ICC数量的变化。Background: The pathogenesis of slow transit constipation is unknown in most cases, The interstitial cells of Cajal (ICCs) have been increasingly recognized as the cells acting as gastrointestinal pacemaker and neurotransmitter mediator. Furthermore, the abnormal changes of the number and structure of ICC have been described in a variety of gastrointestinal motility disorders. Aims: To appraise the changes of ICCs in colonic tissue of slow-transit colonic motility mouse model. Methods: The mouse model was constructed by subcutaneous injection of morphine. Proximal and distal colonic tissues were obtained and the expression and distribution of ICCs were observed by immunohistochemistry, c-Kit protein and c-kit mRNA were detected by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Results: (1) In the proximal colonic tissues, the surface area of c-kit positive cells in the test groups decreased significantly compared with that in the control group (P〈0.01), and that in the test group Ⅱ was less than that in the test group I after 45 days (P〈0.01). The surface area of c-kit positive cells in the group after stopping of morphine was less than that in the groups given naloxone and in the control group after 60 days (P〈0.01). There were no differences between all test groups and the control group in the surface area of c-kit positive cells of distal colonic tissue. (2)In the proximal colonic tissue, the c-Kit protein and c-kit mRNA in the test groups decreased significantly when compared with the control group after 45 days (P all 〈0.01). The levels of c-Kit protein and the expression of c-kit mRNA in the group after stopping of morphine were lower than those in the groups given naloxone and in the control group, respectively after 60 days (P〈 0.05 and P〈0.01). Conclusions: The amount of c-kit positive cells, c-Kit protein and c-kit mRNA decreased obviously in the proximal colonic tissue of morphine-induced slow-transit
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