普芦卡必利对慢传输型便秘大鼠胃肠道传输功能及胃肠道肌层ICC的影响

发布时间：2018-04-01 14:37

  本文选题：慢传输型便秘　切入点：大黄酸　出处：《河北北方学院》2014年硕士论文

【摘要】：慢传输型便秘（slow transit constipation，STC）是由结肠运动紊乱所致，以结肠通过时间延长和结肠动力下降为特征的一类顽固性便秘。因STC的病因、发病机制尚未完全清楚，所以一直是临床上治疗的难题。2012年12月上市的普芦卡必利（Prucalopride），是一类高选择性5-羟色胺4受体（5-hydroxtrptamine receptor4，5-HT4）激动剂，临床研究已证实其可改善便秘相关的胃肠道症状，对慢性便秘的疗效显著。但普芦卡必利对在STC疾病过程中表现为数量减少和功能异常的胃肠道起搏细胞—Cajal间质细胞（interstitial cell of Cajal，ICC）是否有恢复及治疗作用，目前尚未见报道。故本课题旨在观察普芦卡必利对慢传输型便秘大鼠胃肠道传输功能及胃肠道肌层中ICC数量及体积的影响，进一步探讨其治疗慢性便秘的机制。 选取健康雄性Wistar大鼠33只，按照完全随机的方法分为对照组、便秘组和治疗组，每组11只。对照组给予生理盐水灌胃。便秘组和治疗组给予大黄酸粉悬液灌胃，建立STC动物模型。造模结束后，对照组和便秘组大鼠采用活性炭悬液灌胃法检测首粒黑便排出时间，，黑色半固体营养糊灌胃法测定胃动力及小肠传输功能，免疫组化染色法观察胃肠道肌层中ICC数量及体积改变。治疗组大鼠给予普芦卡必利悬液灌胃治疗，2W后采用上述方法进行首粒黑便排出时间、胃动力及小肠传输功能的测定，及免疫组化染色观察ICC数量及体积改变。 胃肠道传输功能相关结果：造模完成后，对照组和便秘组大鼠的首粒黑便排出时间分别为（343.55±103.84）min，（471.43±59.43）min；胃残留量分别为（0.88±0.126）g，（1.60±0.20）g；活性炭末推进长度分别为（69.10±4.23）cm，（45.40±3.24）cm。便秘组大鼠的首粒黑便排出时间、胃残留率、活性炭末推进长度分别与对照组进行统计学分析，发现差异均有统计学意义（P0.05）。普芦卡必利治疗后，治疗组大鼠的首粒黑便排出时间为（351.04±100.05）min，活性炭末推进长度为（66.00±9.07）cm，与便秘组比较，有统计学差异（P0.05）；治疗组大鼠的胃残留量为（1.54±0.23）g，与便秘组比较无明显改善。胃肠道ICC相关结果分析：造模完成后，对照组和便秘组大鼠胃窦中c-kit阳性细胞面积比较，无统计学差异（P0.05）。便秘组大鼠小肠、结肠肌层c-kit阳性细胞面积明显小于对照组，差异有统计学意义（p0.01）。普芦卡必利治疗后，治疗组大鼠小肠肌层中c-kit阳性细胞面积略有增大，但与便秘组比较，无统计学差异（P0.05）；治疗组大鼠结肠肌层c-kit阳性细胞面积为（24778.88±2951.16）μm2，与便秘组组大鼠结肠肌层c-kit阳性细胞面积（16305.86±5454.73）μm2比较，有统计学差异（p0.01）。 本实验研究发现：慢传输型便秘是一种全胃肠道动力障碍性疾病，其发病机制可能与小肠、结肠中ICC体积的减小直接相关，而与胃窦中ICC改变无明显相关性。新型5-HT4激动剂—普芦卡必利主要作用于结肠，可改善便秘大鼠结肠中ICC的体积及形态，推测其对便秘大鼠肠道传输功能的改善作用可能部分是通过恢复肠道组织中ICC体积与功能达到的。
[Abstract]:Slow transit constipation (slow transit, constipation, STC) is caused by colonic motility disorder in the colon through a kind of intractable constipation characterized by decreased time and colonic motility. Because STC etiology, pathogenesis is unclear, so it has been a difficult problem in the treatment of clinical.2012 in December listed Pu Lu card will Li (Prucalopride), is a kind of highly selective 5- HT 4 receptor (5-hydroxtrptamine receptor4,5-HT4) agonist, clinical research has confirmed that it can improve constipation related gastrointestinal symptoms, curative effect on the treatment of chronic constipation significantly. But the general card will Lu in STC disease process to reduce the number of Cajal and gastrointestinal dysfunction tract pacemaker cells of mesenchymal cells (interstitial - cell of Cajal, ICC) whether the recovery and treatment effect, has not yet been reported. So this research aims to investigate the general Lu card will benefit on slow transit constipation type The effect of the transmission function of the stomach and intestines of the rat and the quantity and volume of ICC in the myometrium of the gastrointestinal tract was discussed, and the mechanism for the treatment of chronic constipation was further explored.
Selected 33 healthy male Wistar rats, randomly divided into control group, constipation group and treatment group, 11 rats in each group. The control group was given normal saline. The constipation group and treatment group were given rhubarb powder suspension gavage, the establishment of STC animal model. After the modeling, and the control group constipation in rats by using activated carbon suspension gavage method detected the first time of defecation, determination of gastric motility and intestinal transmission function of black semisolid nutrient paste gavage method, immunohistochemical staining was used to observe the gastrointestinal tract in the muscular layer of the ICC number and volume change. The treatment group rats were given general Lu card will hang gavage, 2W after adopting the method of the first black grain discharge time, determination of gastric motility and intestinal transmission function, and immunohistochemical staining to observe the changes of the number and volume of ICC.
鑳冭偁閬撲紶杈撳姛鑳界浉鍏崇粨鏋滐細閫犳ā瀹屾垚鍚

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