Wang Xin, Zhong Yue-Xia, Lan Mei, Zhang Zong-You, Shi Yong-Quan, Lu Ju, Ding Jie, Wu Kai-Cun, Jin Jian-Ping, Pan Bo-Rong, Fan Dai-Min
Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University,Xi'an 710033,Shaanxi Province,China.
World J Gastroenterol. 2002 Feb;8(1):162-7. doi: 10.3748/wjg.v8.i1.162.
To isolate the proteins involved in pharmacologic action of senna extract (SE) from mouse gastrointestinal tract and to explore the molecular mechanism of gastrointestinal motility change induced by SE.
SE was administrated to mice by different routes. Gastrointestinal motility of mice was observed using cathartic, gastrointestinal propellant movement experiments and X-ray analysis. Mouse model for gastrointestinal motility enhancement was established through continuous gastric administration of SE at progressively increased dose. At 3 h and week 3, 4, 6 and 10, morphological changes of gastrointestinal tissues were found under light microscope. Ultrastructural changes of intestinal and colonic tissues at week 6 were observed under transmission electron microscope. The colonic proteomic changes in model mice were examined by two-dimension polyacrylamide gel electrophoresis with immobilized pH gradient isoelectric focusing to screen the differentially expressed proteins, and their molecular masses and isoelectric points were determined. Two N-terminal sequences of the samples were also determined by mass spectrometry.
SE (0.3g) caused diarrhea after gastric administration in 1-6h and enhanced gastrointestinal propellant (65.1+/-7.5%; 45.8+/-14.6%, P<0.01) in mice, but intramuscular and hypodermic injection had no cathartic effect. X-ray analysis of gastrointestinal motility demonstrated that gastric administration of SE enhanced gastric evacuation and gastrointestinal transferring function. At 3 h and week 3 and 4 after gastric administration of SE, light microscopic examination revealed no apparent change in gastrointestinal mucosal tissues, but transmission electron microscopic examination revealed inflammatory changes in whole layer of intestinal and colonic wall. Twenty differential proteins were detected in the colonic tissues of the model mice by two-dimensional electrophoresis, and the N-terminal amino acid sequences of two proteins were determined.
SE causes diarrhea and enhances gastrointestinal motility through digestive tract administration. Long-term gastric administration of SE induces inflammatory changes and cell damage in the whole gastrointestinal tract. The differential proteins screened from the colonic tissues of the model mice might mediate the enhancing effect of SE on gastrointestinal motility.
从小鼠胃肠道中分离出参与番泻叶提取物（SE）药理作用的蛋白质，并探讨SE诱导胃肠动力改变的分子机制。
通过不同途径给小鼠给予SE。采用泻下、胃肠推进运动实验及X射线分析观察小鼠的胃肠动力。通过连续胃内给予逐渐增加剂量的SE建立小鼠胃肠动力增强模型。在给药后3小时以及第3、4、6和10周，在光学显微镜下观察胃肠道组织的形态学变化。在第6周，在透射电子显微镜下观察小肠和结肠组织的超微结构变化。通过固定化pH梯度等电聚焦二维聚丙烯酰胺凝胶电泳检测模型小鼠结肠蛋白质组变化，以筛选差异表达蛋白质，并确定其分子量和等电点。还通过质谱法测定样品的两个N端序列。
胃内给予SE（0.3g）在1 - 6小时后引起腹泻，并增强小鼠胃肠推进力（65.1±7.5%；45.8±14.6%，P<0.01），但肌肉注射和皮下注射无泻下作用。胃肠动力的X射线分析表明，胃内给予SE可增强胃排空和胃肠转运功能。胃内给予SE后3小时以及第3和4周，光学显微镜检查显示胃肠道黏膜组织无明显变化，但透射电子显微镜检查显示小肠和结肠壁全层有炎症改变。通过二维电泳在模型小鼠结肠组织中检测到20种差异蛋白质，并确定了两种蛋白质的N端氨基酸序列。
SE通过消化道给药引起腹泻并增强胃肠动力。长期胃内给予SE可诱导全胃肠道的炎症改变和细胞损伤。从模型小鼠结肠组织中筛选出的差异蛋白质可能介导SE对胃肠动力的增强作用。
