传统沙生蒙药—沙葱、沙芥改善功能性消化不良的药效物质及其作用机制研究

Functional dyspepsia (FD) mainly shows gastrointestinal motility disorders. It is well known that brain-gut peptide (BGP) dysfunctional is a dominant reason of FD. FD is difficult to cure, with a high recurrent rate. Until now, there is no medication can be used as direct target to FD in clinic..The digestive system disease is one of the supermacy diseases in the Mongolian Medicine. In the prevention and treatment of dyspepsia, traditional arenicolous Mongolian Medicine, Allium mongolicum and Pugionium cornutum have accumulated rich experience and knowledge of promoting gastrointestinal motility and improving indigestion..Previous research results indicated A. mongolicum and P. cornutum had the activity of improving FD. However, the effective substances and mechanism of them are unclear yet. On the basis of preliminary work, this project will summarize the fragmentation pattern of various constituents, combine with LC-MS, LC-MS/MS and GC-MS fingerprint analysis results to carry out a rapid prediction, isolation and identification of effective components in the first; and in the second, the animal model consistent with the pathogenesis of FD and ICC cell model will be used to research the effect and mechanism of improving FD on the basis of regulating the gastrointestinal motility disorder and the core link of BGP level disorder. On the basis of above mentioned experiments, the project will clarify the effective substances and functional dyspepsia-improving mechanism of A. mongolicum and P. cornutum. The results will provide a scientific basis for guiding reasonable application of A. mongolicum and P. cornutum in the clinical Mongolian Medicine and provide the foundation for the development of ethnic medicine from clinical. And which will be benefit for promoting the development of sand industry.

功能性消化不良（FD）主要表现为胃肠运动障碍，脑肠肽功能失调为其主要发病机制。至今尚无关于FD的针对性治疗药物，使得该病难以治愈，复发率高。.消化系统疾病是蒙医药学的优势病种之一。传统沙生蒙药沙葱、沙芥在预防和治疗消化不良方面积累了丰富的知识和经验。.课题组前期研究结果表明沙葱、沙芥具有改善FD的作用，但药效物质研究不够深入，作用机制尚待明确。本项目拟在前期工作基础上，总结各类化学成分的质谱裂解规律，结合LC-MS、LC-MS/MS、GC-MS等指纹图谱分析结果，进行药效成分的快速预测、分离与鉴定，综合利用波谱技术确定药效物质的结构；采用与FD发病机制、临床表现相吻合的动物模型及ICC细胞模型，基于改善胃肠动力障碍、调节FD发病核心环节—脑肠肽水平紊乱，阐明沙葱、沙芥改善FD的药效物质及作用机制，指导二者在蒙医药临床的合理应用，为源于临床的民族医药的研发奠定基础，促进沙产业发展。

功能性消化不良（FD）主要表现为胃肠运动障碍，脑肠肽功能失调为其主要发病机制。.本项目以给药大鼠胃排空、碳粉推进长度及离体小肠组织灌流实验的测定结果作为导向。综合应用多种波谱和色谱技术，分别从沙葱和沙芥中分离鉴定39和31个单体成分。其中，沙葱中主要含有黄酮和酚酸，而沙芥中主要成分为含氮和含硫的化合物。.灌胃给予FD模型小鼠沙葱提取物，检测其对小鼠的体重、排便以及小肠内碳粉推进长度的影响；采用Elisa法检测血清中与胃动素的含量；采用H&E染色法，观察结肠的病理切片；采用Real-time PCR及Western blot实验方法，检测与肠道运动有关的多种基因和蛋白的表达。研究发现沙葱提取物能够增加便秘小鼠粪便排泄量、小肠内碳粉推进长度、血清中MTL的含量；能够明显增加小鼠结肠壁厚度，增加腺体内杯状细胞数量。首次明确其作用机制一方面可能是通过减少AQP3表达，增加结肠内水通量，进而软化大便；另一方面通过下调Gα、p-PI3K及上调c-kit、SCF、PI3K的表达，促进小肠运动，进而发挥改善FD的作用。.结合化学成分系统性研究结果、LC-MS/MS分析结果以及离体小肠灌流法对单体化合物的筛选结果，推测黄酮及酚酸类成分为沙葱改善FD的活性物质。采用离体组织灌流法及HCT116细胞模型，通过加入胃肠受体抑制剂，研究活性单体成分改善FD的作用机制。明确其作用机制可能与激活M胆碱受体、μ阿片受体拮抗剂、5-HT受体、钙离子通道及IP3受体有关。.采用类似的方法，首次通过体内实验，明确了沙芥改善小鼠功能性消化不良的作用，其机制可能是一方面通过上调胃动素、促进排泄，改善小鼠功能性消化不良；另一方面通过下调Gα及上调c-kit、SCF、PI3K基因的表达，促进小肠运动，进而对小鼠功能性消化不良有一定的缓解作用。采用离体小肠灌流法对单体化合物的筛选结果，推测含氮、含硫类成分为沙芥改善功能性消化不良的活性物质，其作用机制可能与激活M胆碱受体、μ阿片受体拮抗剂受体有关。.通过本项目的研究，基本阐明了蒙药沙葱和沙芥改善FD的药效物质。其实施将为源于临床的民族医药的研发奠定基础，促进沙产业发展。.发表科研论文14篇，申请发明专利2项，培养研究生7人。