结肠粘液分泌异常是导致便秘的重要原因。大黄的泻下作用可缓解便秘，但长期和短期使用疗效差异明显，且机制不清。本课题组前期研究发现，长期使用大黄可导致动物对药物的敏感性降低，但短期效果显著。本研究拟在此前期研究的基础上，通过制备大鼠便秘模型，运用短路电流和离子浓度同步检测等技术，进行杯状细胞功能检测和粘液分泌测定，以探讨大黄对结肠粘液分泌和膜屏障变化调节；采用糖分子探针和荧光球标记技术测定粘液和粘膜的通透性；使用免疫荧光和蛋白印记，以结肠紧密连接蛋白和Fn、MMP-9和MMP-2变化为指标，探讨大黄对粘液分泌的双向调控作用机制；利用定向敲除基因技术，观察肥大细胞对离子分泌、粘液屏障的调节作用，探讨肥大细胞在大黄润肠通便中的作用。通过研究证明我们的假说：“大黄促进结肠粘液分泌和粘膜屏障保护的作用，具有肥大细胞和神经通路依赖性”，以揭示大黄短期使用的优势，为降低长期使用大黄毒副作用提供理论依据。

Colonic mucus secretion abnormality is an important cause of constipation. The purgative effect of Rhubarb can relieve constipation, but curative effect of long and short term is different and its mechanism is not clear. .Our previous studies showed that long-term use of rhubarb could lead to reduced sensitivity to the drug, but the short-term effect is significant as well. Base on the preliminary investigation, in order to evaluate the effect of rhubarb on colonic mucus secretion and membrane barrier , the function of goblet cells and mucus secretion was studied with the short-circuit current and ion concentration synchronous detection technology on the rat constipation model. In order to conform the permeability of mucus and mucosa on the some substance, the sugar molecular probes and fluorescent lamps marker were used. To research the regulation mechanism of rhubarb on bidirectional mucus secretion, it need to using immunofluorescence and Western blotting so as to indicate the change of tight junction proteins, Fn, MMP-9 and MMP-2. In order to study the effect of the mast cells on ion secretion and regulation mucus barrier in colon the directional gene knockout technology will be used and the mechanism of rhubarb on the loosening bowel to relieve constipation researched ..The purpose of the study is to identify our hypothesis“ Rhubarb could promote colonic mucus secretion and mucosal barrier protective role, which has been dependence the mast cells and nerve pathway”. All the investigation is to reveal the advantages of the short-term use of Rhubarb and decrease side effects of the long-term use. We wish it could provide a theoretical basis for the clinical researchers.