包云光，李小兵，赵 婵

(金华市中心医院，浙江 金华 321000)

·基础与临床研究·

复方苯乙哌啶对大鼠肠传输功能、病理和神经递质的远期影响

包云光，李小兵，赵 婵

(金华市中心医院，浙江 金华 321000)

目的： 通过建立大鼠便秘模型，探讨复方苯乙哌啶对大鼠肠传输功能、病理组织学和神经递质的远期影响及其安全性。方法给健康Wistar大鼠饲喂含复方苯乙哌啶的混悬液为实验组，饲喂普通水作为对照。饲养90天后停药1周，测定肠道传输功能；观察结肠大体形态和病理组织学检查；测定结肠黏膜NO、SP含量及VIP阳性细胞分布情况。结果实验组大鼠日均粪便粒数小于对照组(P<0.001)；实验组大鼠首粒黑便排出时间慢于对照组 (P<0.05)。造模第5天、第90天2组间平均体重差异无统计学意义。2组大鼠结肠黏膜光镜下病理组织学表现类似。结肠黏膜NO、SP含量、VIP阳性细胞分布2组间差异无统计学意义。结论复方苯乙哌啶较长期使用可致肠道传输速度明显减慢，造成顽固便秘, 但对肠黏膜组织病理及肠神经系统递质NO、 SP、VIP的产生均无明显远期影响。

复方苯乙哌啶；传输功能；病理；神经递质；远期影响

Abstract: [Objective] This study was designed to evaluate long-term effects of diphenoxylate on the intestinal transport function, colonic histopathology and the neurotransmitter, and provide a basis for further evaluation of the safety of its clinical application. [Method] Healthy Wister rats were divided randomly into control group and constipation group. In constipation group, the rats were daily administered diphenoxylate to develop slow transit constipated model, while the control rats taken without any drugs. The fecal number, fecal weight and body weight of rats were recorded. Transit functions of intestinal movement were examined. The levels of NO, SP were measured, and the distribution of VIP positive cells was observed. [Result]The fecal number daily in the constipated group was decreased significantly than that in controls (P<0.001). The time of discharge of the first black faeces ，significantly longer than that in controls (P<0.05). The average body weight on the first five days, the 90 days between the two groups had no significant difference. No obvious differences of colonic histopathologic manifestations were observed between the two groups. The differences of NO, SP levels and density of VIP positive cells in distal colonic segment between the two groups had not reached significance. [Conclusion]Diphenoxylate can slow intestinal transit function after longer-term administration, resulting in intractable constipation, but had no histopathological damage on the colonic mucosa，and had no significant long-term effects on the enteric nervous system of NO, SP, and VIP neurotransmitter production.

Keywords: diphenoxylate; intestinal transit function; pathology; neurotransmitters; long-term effects

复方苯乙哌啶(Diphenoxylate)为盐酸地芬诺酯和硫酸阿托品复合制剂，主要作用于U型阿片受体，对中枢神经系统产生镇静、镇痛作用，降低内脏的敏感性，提高胃肠平滑肌的张力，其止泻、缓解腹痛效果明显，见效快，被临床尤其基层广泛应用。长期服用可成瘾,大剂量可致欣快感，过量可致严重的呼吸抑制和昏迷[1]。本研究通过建立大鼠模型，观察体重、大便、病理组织学的变化，测定肠道传输功能和结肠黏膜NO、SP含量，及VIP的分布情况，以了解复方苯乙哌啶较长期使用对肠道传输功能、病理组织学和神经递质、以及机体的远期影响，为进一步评价其临床应用的安全性提供依据。

1 对象与方法

1.1 研究对象

32只健康Wistar大鼠，雄性，6～8周龄，体重110～130g，由上海斯莱克实验动物有限公司提供，生产许可证号SCXK(沪)2007-0005，随机分为对照组16只和实验组16只。……