摘要
目的:观察洛哌丁胺构建的大鼠便秘模型中水通道蛋白家族中AQP3和AQP8蛋白及其mRNA定量表达,探讨洛哌丁胺构建大鼠便秘模型对AQP3和AQP8的影响.方法:SD♂大鼠30只,随机分为5组,造模开始时处死1组大鼠,检测结肠传输功能及结肠组织的AQP3,8表达水平,作为基准参考线.剩余4组予以洛哌丁胺1.5 mg/(kg·d)灌胃,诱导造模.分别于造模的第3、7天和造模成功后第3、7天各处死一组模型大鼠,检测结肠传输及AQP3,AQP8蛋白及其mRNA定量表达.结果:大鼠粪便含水量在诱导便秘模型的过程中明显减少,停药后7 d,粪便内的水分并不能自发恢复至正常(2.29 g±1.17 g vs 0.80 g±0.27 g,P=0.01<0.05).试验过程中,大鼠结肠传输功能未发生改变(67.72%vs 58.64%,P=0.971>0.05).AQP8远端表达停药7 d上升,与造模7 d时相比,差异有统计学意义(0.43±0.31vs 2.66±0.87,P=0.008).AQP8近端表达给药后迅速上升至较高水平,与正常组对照具有统计学意义(15.96±2.13,P=0.00),停药7 d后其表达再次上升,与给药7 d相比,差异有统计学意义(6.37±0.23 vs 0.79±0.13,P=0.015).停药后,AQP3在结肠近端持续表达下降,与正常对照组相比,差异有统计学意义(0.20±0.06,P=0.04).结论:洛哌丁胺能够提高模型大鼠结肠AQP8表达,促进肠道跨膜水运输,减少粪便含水量而导致便秘.
AIM: To observe the differential expression of AQP3 and 8 in loperamide induced constipation in rats, and to explore the role of these two proteins in constipation.METHODS: Thirty male SD rats were randomly divided into five groups. One group was killed at the beginning to measure intestinal transit function and the expression of AQP3 and 8 in human colonic epithelial cells as basic references. Loperamide [1.5 mg/(kg?d)] was given by intragastric administration in the remaining four groups of rats to induce constipation. Two groups of rats were killed on days 3 and 7 after initial loperamide administration, respectively, while the other two groups were killed 3 and 7 d after last loperamide administration, respectively. Intestinal transmission function was determined, and the expression of AQP3 and 8 was detected. RESULTS: Intestinal transit function kept stable(67.72% vs 58.64%, P〈0.05) throughout the experimental process, while fecal water content decreased. The fecal water content could not return to normal 7 d after stopping loperamide(2.29 g ± 1.17 g vs 0.80 g ± 0.27 g, P = 0.01). AQP8 expression in the proximal colon had an upward trend 3 to 7 d after the initial loperamide administration, greatly higher than that in the normal control group(P = 0.00). Seven days after stopping loperamide, AQP8 had a rising trend in both the proximal and distal colons(0.43 ± 0.31 vs 2.66 ± 0.87, P = 0.008), while AQP3 expression declined(6.37 ± 0.23 vs 0.79 ± 0.13, P = 0.015). CONCLUSION: Loperamide enhances the expression of AQP8 in the intestine of rats, which facilitates water movement across the membrane. Deficient water absorption may play a role in the pathogenesis of loperamide induced constipation.
出处
《世界华人消化杂志》
CAS
北大核心
2014年第7期969-974,共6页
World Chinese Journal of Digestology
基金
江苏省六大人才高峰重点课题基金资助项目
No.2011-WS40
国家自然科学基金资助项目
No.81373645
江苏省中医药管理局课题基金资助项目
No.LZ11042~~