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普蘆卡必利對慢傳輸型便秘大鼠胃腸道傳輸功能及胃腸道肌層ICC的影響

發(fā)布時間:2018-04-01 14:37

  本文選題:慢傳輸型便秘 切入點:大黃酸 出處:《河北北方學(xué)院》2014年碩士論文


【摘要】:慢傳輸型便秘(slow transit constipation,STC)是由結(jié)腸運動紊亂所致,以結(jié)腸通過時間延長和結(jié)腸動力下降為特征的一類頑固性便秘。因STC的病因、發(fā)病機制尚未完全清楚,所以一直是臨床上治療的難題。2012年12月上市的普蘆卡必利(Prucalopride),是一類高選擇性5-羥色胺4受體(5-hydroxtrptamine receptor4,5-HT4)激動劑,臨床研究已證實其可改善便秘相關(guān)的胃腸道癥狀,對慢性便秘的療效顯著。但普蘆卡必利對在STC疾病過程中表現(xiàn)為數(shù)量減少和功能異常的胃腸道起搏細胞—Cajal間質(zhì)細胞(interstitial cell of Cajal,ICC)是否有恢復(fù)及治療作用,目前尚未見報道。故本課題旨在觀察普蘆卡必利對慢傳輸型便秘大鼠胃腸道傳輸功能及胃腸道肌層中ICC數(shù)量及體積的影響,進一步探討其治療慢性便秘的機制。 選取健康雄性Wistar大鼠33只,按照完全隨機的方法分為對照組、便秘組和治療組,每組11只。對照組給予生理鹽水灌胃。便秘組和治療組給予大黃酸粉懸液灌胃,建立STC動物模型。造模結(jié)束后,對照組和便秘組大鼠采用活性炭懸液灌胃法檢測首粒黑便排出時間,,黑色半固體營養(yǎng)糊灌胃法測定胃動力及小腸傳輸功能,免疫組化染色法觀察胃腸道肌層中ICC數(shù)量及體積改變。治療組大鼠給予普蘆卡必利懸液灌胃治療,2W后采用上述方法進行首粒黑便排出時間、胃動力及小腸傳輸功能的測定,及免疫組化染色觀察ICC數(shù)量及體積改變。 胃腸道傳輸功能相關(guān)結(jié)果:造模完成后,對照組和便秘組大鼠的首粒黑便排出時間分別為(343.55±103.84)min,(471.43±59.43)min;胃殘留量分別為(0.88±0.126)g,(1.60±0.20)g;活性炭末推進長度分別為(69.10±4.23)cm,(45.40±3.24)cm。便秘組大鼠的首粒黑便排出時間、胃殘留率、活性炭末推進長度分別與對照組進行統(tǒng)計學(xué)分析,發(fā)現(xiàn)差異均有統(tǒng)計學(xué)意義(P0.05)。普蘆卡必利治療后,治療組大鼠的首粒黑便排出時間為(351.04±100.05)min,活性炭末推進長度為(66.00±9.07)cm,與便秘組比較,有統(tǒng)計學(xué)差異(P0.05);治療組大鼠的胃殘留量為(1.54±0.23)g,與便秘組比較無明顯改善。胃腸道ICC相關(guān)結(jié)果分析:造模完成后,對照組和便秘組大鼠胃竇中c-kit陽性細胞面積比較,無統(tǒng)計學(xué)差異(P0.05)。便秘組大鼠小腸、結(jié)腸肌層c-kit陽性細胞面積明顯小于對照組,差異有統(tǒng)計學(xué)意義(p0.01)。普蘆卡必利治療后,治療組大鼠小腸肌層中c-kit陽性細胞面積略有增大,但與便秘組比較,無統(tǒng)計學(xué)差異(P0.05);治療組大鼠結(jié)腸肌層c-kit陽性細胞面積為(24778.88±2951.16)μm2,與便秘組組大鼠結(jié)腸肌層c-kit陽性細胞面積(16305.86±5454.73)μm2比較,有統(tǒng)計學(xué)差異(p0.01)。 本實驗研究發(fā)現(xiàn):慢傳輸型便秘是一種全胃腸道動力障礙性疾病,其發(fā)病機制可能與小腸、結(jié)腸中ICC體積的減小直接相關(guān),而與胃竇中ICC改變無明顯相關(guān)性。新型5-HT4激動劑—普蘆卡必利主要作用于結(jié)腸,可改善便秘大鼠結(jié)腸中ICC的體積及形態(tài),推測其對便秘大鼠腸道傳輸功能的改善作用可能部分是通過恢復(fù)腸道組織中ICC體積與功能達到的。
[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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