润肠通便药物筛选小鼠模型的选择及药效评价研究  

Mice models selection and in vivo evaluation of anti-constipation drugs

作　　者：闵翅驹 黄晓星[1,2] 王生 田华洁[1,2] 刘莉 

机构地区：[1]中国医药工业研究总院药理评价研究中心,上海200040 [2]上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200437 [3]上海市生物物质成药性评价专业技术服务中心,上海200437

出　　处：《世界临床药物》2015年第6期405-409,413,共6页World Clinical Drug

摘　　要：目的建立机制不同的润肠通便药物筛选小鼠模型,探讨作用于不同靶点的药物对动物模型的选择性,为新药开发提供基础。方法以复方地芬诺酯和多巴胺分别诱导机制不同的小鼠便秘模型,选择纳洛酮和伊托必利作为工具药,以小鼠小肠推进率为指标,考察机制不同的动物模型是否只适用于对应靶点润肠通便药物的筛选。在此基础上,考察伊托必利和麻仁润肠丸两个工具药对正常小鼠小肠推进率的影响,以探讨正常小鼠能否用于润肠通便药物的筛选。结果复方地芬诺酯可显著抑制小鼠小肠推进,而纳洛酮可显著对抗复方地芬诺酯对小肠推进的抑制作用,但伊托必利无类似的明显拮抗作用。对于多巴胺诱导的便秘模型,伊托必利能有效促进多巴胺诱导的便秘模型小鼠的小肠推进。伊托必利和麻仁润肠丸均能明显促进正常小鼠的小肠推进率。结论作用机制不同的润肠通便药物筛选对动物模型具有一定的选择性,进行润肠通便药物作用评估筛选时,应采用相对应作用靶点药物复制的小鼠模型。然而针对靶点未知或多靶点作用的药物,可利用正常小鼠进行润肠通便药效筛选。Objective To develop a mice model for anti-constipation drugs screening and to select appropriate animal model for drug evaluation based on drug receptors. Methods Two animal models of acute constipation induced by diphenoxylate(agonist of opioid receptor) and dopamine(agonist of dopamine receptor) in mice were selected in this study. The effects of itopride, naloxone and Maren on small intestinal motility were evaluated. Results Diphenoxylate and dopamine reduced small intestinal motility. Naloxone inhibited the diphenoxylate-induced reduction of small intestinal motility, while itopride had no effect on it. On the other side, itopride significantly inhibited the dopamine-induced reduction in small intestinal motility. In normal mice, both diphenoxylate and dopamine inhibited small intestinal motility. Itopride and Maren stimulated small intestinal motility. Conclusion The stimulation of anti-constipation drugs on small intestinal motility is receptor-dependent. Appropriate animal model needs to be selected according to drug target receptor. Normal animals without drug-induced constipation can be used for anti-constipation drugs prescreening.

关 键 词：润肠通便 复方地芬诺酯 多巴胺 伊托必利 麻仁润肠丸 

分 类 号：R965[医药卫生—药理学]