目的 比较进食含复方地芬诺酯的饲料和用复方地芬诺酯混悬液灌胃复制大鼠慢传输便秘(STC)模型的差异。方法 40只Sprague-Dawley大鼠随机均分为灌胃对照(A)组、灌胃(B)组、饲喂对照(C)组、饲喂(D)组。B组采用复方地芬诺酯混悬液灌胃14 d,A组用等量生理盐水灌胃,D组进食含有复方地芬诺酯的饲料120 d,C组进食普通饲料。造模成功后炭墨灌胃,观察各组肠道炭墨推进率;免疫组织化学方法检测水通道蛋白(AQP) 3、AQP4蛋白含量。结果 A、B组各有2只大鼠死亡。肠道炭墨推进率D组低于B组(P<0.05);AQP3、AQP4蛋白水平D组均高于B组(P<0.05)。结论 进食复方地芬诺酯饲料120 d较复方地芬诺酯灌胃14 d能够更安全、稳定地复制STC模型。AQP可能参与STC的发生、发展。
Objective To compare the rat model of slow transit constipation (STC) established with gavage or feeding compound diphenoxylate. Methods Forty Sprague-Dawley rats were randomly divided into gavage control group (A), gavage group (B), feeding control group (C) and feeding group (D) equally. Group B was given compound diphenoxylate suspension by gavage for 14 days while group A accepted isodose normal saline. Group D were given feed containing compound diphenoxylate for 120 days while group C accepted normal feed. Carbon ink was poured into stomachs to observe the propelling rate after modeling, and the content of aquaporin 3 and aquaporin 4 were detected with immunohistochemistry. Results There were two rats died in group A and group B, respectively. The carbon ink propelling rate was lower in group D than in group B (P<0.05). Both aquaporin 3 and aquaporin 4 were more in group D than in group B (P<0.05). Conclusion STC rat model can be established by eating diphenoxylate feed for 120 days, which is safer and more stable than that of gavage for 14 days. Aquaporins in colons may play a role in onset and development of STC.
[1] 冯雪建,卢占军,高登慧. 大鼠灌胃给药方法的研究[J]. 实验动物科学与管理, 2006, 23(4): 53-55.
[2] 辛玉,张红星,周利. 功能性便秘大鼠模型的研究进展[J]. 湖北中医杂志, 2014, 36(03): 74-76.
[3] 蒲春霞. 水通道蛋白研究进展[J]. 成都大学学报(自然科学版), 2010, 29(2): 104-106.
[4] 尹淑慧,孟荣贵. 水通道与大肠内液体转运及便秘的关系[J]. 国际病理科学与临床杂志, 2005, 25(4): 364-367.
[5] Ramirez-Lorca R, Vizuete ML, Venero JL, et al. Localization of aquaporin-3 mRNA and protein along the gastrointestinal tract of Wistar rats [J]. Pflugers Arch, 1999, 438(1): 94-100.
[6] Zeuthen T. Water-transporting proteins [J]. J Membrane Biol, 2010, 234(2): 57-73.
[7] Laforenza U. Water channel proteins in the gastrointestinal tract [J]. Mol Aspects Med, 2012, 33(5/6): 642-650.
[8] Ikarashi N, Kon R, Iizasa T, et al. Inhibition of aquaporin-3 water channel in the colon induces diarrhea [J]. Biol Pharm Bull, 2012, 35(6): 957-962.
[9] 中华医学会消化病学会胃肠动力学组,中华医学会外科学会结直肠外科肛门学组. 中国慢性便秘诊治指南(2013,武汉)[J]. 胃肠病学, 2013, 18(10): 605-612.
[10] 朱丽明,方秀才,刘诗,等. 全国多中心慢性便秘患者情绪和睡眠状况的调查[J]. 中华医学杂志, 2012, 92(32): 2243-2246.
[11] 张雪芳,徐桂华,陈金珍,等. 便秘的病因及治疗进展[J]. 中华全科医学, 2009, 7(11): 1229-1331.
[12] Zhao GX, Li J, Wang JY, et al. Aquaporin 3 and 8 are down-regulated in TNBS-induced rat colitis [J]. Biochem Biophys Res Commun, 2014, 443(1): 161-166.
[13] 占煜,陈泰宇,唐诗宇,等. 从水通道蛋白3介导的结肠水液代谢思考治疗慢性便秘的药物研究[J]. 川北医学院学报, 2014, 29(6): 542-545.
[14] 赵琼,陈为,汤朝晖,等. 水通道蛋白4与胃肠道疾病[J]. 辽宁中医药大学学报, 2010, 12(1): 35-37.
[15] Ma T, Verkman AS. Aquaporin water channels in gastrointestinal physiology [J]. J Physiol, 1999, 517(2): 317-326.
[16] Wang KS, Ma T, Filiz F, et al. Colon water transport in transgenic mice lacking aquaporin-4 water channels [J]. Am J Physiol Gastrointest Liver Physiol, 2000, 279(2): G463-G470.
[17] 宇永军. 水通道蛋白AQP-1、AQP-4与慢传输型便秘的相关性研究[D]. 石家庄:河北医科大学, 2010.
[18] 赵伟,孙国志. 常用实验动物随机分组方法[J]. 兽牧兽医科技信息, 2009(4): 61-62.
[19] 王晓玲,李亚妮,江梅,等. AQP4、AQP9在便秘小鼠结肠粘膜中的表达[J]. 胃肠病学和肝病学杂志, 2015, 24(4): 421-423.
[20] 钱海华,徐天舒,曾莉,等. 通便颗粒调节慢传输型便秘大鼠结肠水通道蛋白3,水通道蛋白8表达的研究[J]. 中国实验方剂学杂志, 2014, 20(24): 180-184.
[21] Lembo A, Camilleri M. Chronic constipation [J]. N Engl J Med, 2003, 349 (14): 1360-1368.
[22] Shahid S, Ramzan Z, Maurer AH, et al. Chronic idiopathic constipation: more than a simple colonic transit disorder [J]. J Clin Gastroenterol, 2012, 46(2): 150-154.
[23] 丁超,顾红,陈玉根,等. “养阴润肠方”用药分析及其治疗慢传输型便秘药理学探究[J]. 辽宁中医杂志, 2014, 41(11): 2329-2331.
[24] Dinning PG, Zarate N, Hunt LM, et al. Pancolonicspatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation [J]. Neurogastroenterol Motil, 2010, 22(12): e340-e349.
[25] Bharucha AE, Wald AM. Anorectal disorders [J]. Am J Gastroenterol, 2010, 105(4): 786-794.
[26] 李震,郑豪,李国宾. 水通道蛋白1在大鼠慢传输便秘模型结肠黏膜中的表达[J]. 中华实验外科杂志, 2013, 30(6): 1259-1261.
[27] Jung JS, Bhat RV, Preston GM, et al. Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance [J]. Proc Natl Acad Sci USA, 1994, 91: 13052-13056.
[28] 王晓玲,李汀,江梅. 水通道蛋白9在便秘型肠易激综合征患者结肠黏膜表达的研究[J]. 胃肠病学和肝病学杂志, 2015, 24(9): 1095-1097.
[29] Ikarashi N, Ushiki T, Mochizuki T, et al. Effects of Magnesium sulphate administration on aquaporin 3 in rat gastrointestinal tract [J]. Biol Pharm Bull, 2011, 34(2): 238-242.
[30] 辛军,孙天娇,张新,等. 水通道蛋白分子靶向治疗和分子靶向成像研究进展[J]. 中国临床医学影像杂志, 2014, 25(11): 807-810.
