天津医药

• 实验研究 • 上一篇    下一篇

马来酸曲美布汀对慢性胰腺炎大鼠胃肠运动功能的影响

张建,白婕,李强,李志华   

  1. 天津市海河医院
  • 收稿日期:2010-10-09 修回日期:2010-12-18 出版日期:2011-06-15 发布日期:2011-06-15
  • 通讯作者: 张建

The empirical study on Chronic Pancreatitis gastrointestinal motility and the intervention of trimebutine maleate

  • Received:2010-10-09 Revised:2010-12-18 Published:2011-06-15 Online:2011-06-15

PDF (PC)

2130

摘要： 目的：探讨慢性胰腺炎(Chronic pancreatitis, CP)大鼠胃肠道运动功能的变化、机制及马来酸曲美布汀的干预作用。方法：健康Wistar大鼠30只，随机分为对照组、慢性胰腺炎组（模型组）和马来酸曲美布汀组（瑞健组），每组l0只。应用油酸经胰胆管灌注的方法制作CP模型，6周后成模，瑞健组给予瑞健溶液灌胃,剂量为2ml/100g，每日一次；模型组及对照组灌注等量的生理盐水，共2周。分别检测各组肠运动系数、血清胆囊收缩素(cholecystokinin，CCK)水平；观测胃窦及小肠环行平滑肌肌条收缩能力、环行平滑肌细胞收缩反应的变化；测定胃肠肌层诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS) mRNA的表达量和平滑肌细胞培养基中一氧化氮(Nitric Oxide, NO)含量的变化。结果：与对照组比较，模型组大鼠肠运动系数降低，胃窦及小肠环行平滑肌条收缩能力、环行平滑肌细胞收缩反应明显下降(P<0.05)，血清CCK水平，iNOS mRNA的表达量，细胞培养基中NO含量均明显升高(P<0.05)。瑞健组和对照组相比差异无统计学意义。结论：慢性胰腺炎可导致大鼠CCK分泌增加，而CCK通过上调胃窦及小肠肌层iNOS mRNA的表达并产生过量的NO，抑制胃肠道环行平滑肌的收缩能力可能是慢性胰腺炎胃肠运动功能障碍的机制之一；而马来酸曲美布汀可以通过抑制CCK释放，下调肌层iNOS mRNA的表达并降低NO产量，从而有效的改善CP所致的胃动力障碍。

关键词: 慢性胰腺炎, 胃肠运动功能, 胆囊收缩素, 一氧化氮

Abstract: ABSTRACT Objective: To explore the changes and mechanismof gastriointestinal motility in the rats with chronic pancreatitis and the intervention effect of trimebutine maleate. Methods: Thirty wistar rats were divided into control,model and trimebutine maleate group randomly(n=10). Rats in model group were used to induce chronic pancreatitis by injecting oleic acid into the pancreatic duct. The control and model groups, administered intragastrically with physiological saline everyday. the Trimebutine Maleate group, administered intragastrically with Trimebutine Maleate everyday. The experiment period of each group are twe weeks. Eight weeks later, bowel movement coefficient and serum cholecystokinin(CCK) were detected, contractility of gastrointestinal circular muscle stripe and the contractile response of dispersed gastrointestinal circular smooth muscle cells stimulated by Aceylcholine (Ach) were measured. RT-PCR was used to detect the expression of inducible nitric oxide synthase (iNOS), mRNA within gastrointestinal muscularis , the level of nitric oxide (NO) in cell cultures was quantified. Results: The bowel movement coefficient, gastrointestinal circular smooth muscle stripes contractility and contractile response of dispersed circular smooth muscle cells stimulated by Ach in model group were declined obviously than the control(P<0.05) while the levels of serum CCK, iNOS mRNA expression and NO production were significantly elevated(P<0.05). Conclusions: Elevated CCK secretion caused by CP up-regulated the expression of iNOS mRNA and increased the output of NO within the gastrointestinal muscularis. It might be one of the mechanisms of gastrointestinal motility dysfunction in CP that NO inhibited the contractility of gastrointestinal circular smooth muscle. The trimebutine maleate can improve the gastrointestinal motility dysfunction caused by CP efficiently, by inhibiting the release of CCK.

Key words: chronic pancreatitis, gastrointestinal motility, cholecystokinin, NO