基于PK-PD模型木香肠粘膜保护作用与气体信号分子体系相关性研究

项目名称： 基于PK-PD模型木香肠粘膜保护作用与气体信号分子体系相关性研究

项目编号： No.81503467

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张静泽

作者单位： 中国人民武装警察部队后勤学院

项目金额： 18万元

中文摘要： 木香是胃肠功能调节中使用频次最高的中药之一，本课题组首次发现木香抑制肠运动与拮抗气体信号分子合成酶抑制剂作用有关，推断内源性气体信号分子的生成可能参与木香对胃肠功能的调节；尚发现木香对化疗药所致肠粘膜损伤具有极强的保护作用，而这种保护作用是否与内源性气体信号分子存在相关性未见报道。稳定的气体信号分子水平及其合成酶表达对胃肠道粘膜保护起至关重要的作用，而“气体信号分子三驾马车”理论认为气体信号分子一氧化氮、一氧化碳及硫化氢作为整体在发挥作用，此与中医药整体治疗理念相吻合。我们认为中药发挥作用亦非对单一一种气体信号分子产生调节，而是整个体系共同作用的结果，对此目前尚未有研究证实。本项目将“气体信号分子三驾马车”的理论首次引入中药胃肠粘膜保护作用机制研究，通过PK-PD模型探讨木香及主要成分对肠粘膜保护作用与气体信号分子整体调控体系的相关性，为中医药胃肠粘膜保护作用研究提供新的理论和方法。

中文关键词： 肠粘膜损伤；木香；；倍半萜；气体信号分子；药物代谢动力学-药物效应动力学

英文摘要： Radix Aucklandiae is one of the most commonly used traditional Chinese medicines in the gastrointestinal regulation. It exhibited a significant and concentration-dependent inhibition activity on the gastrointestinal contractions induced by potassium chloride and acetylcholine, whereas, the spasmolytic response of Radix Aucklandiae was reverted in the presence of the gaseous signal molecule synthases inhibitors. According to the results, we presume that antispasmodic ingredients in Radix Aucklandiae may be involved in the regulation of gastrointestinal motility through the pathway of endogenous gaseous signal molecules. And Radix Aucklandiae showed a strong protection of intestinal mucosa injury. There has no report involved in the interaction between the protections of intestinal mucosa injury of Radix Aucklandiae and gaseous signal molecules. Results of recent researches in digestive system proved that stable levels of gaseous molecules and the expression of relevant synthases play crucial roles for the regulation of gastrointestinal physiological functions. We believe that it necessary to examine the biological and potential therapeutic effects of these gases as a type theory of “gaseous triumvirate”. These three gases form what has come to be known as the whole system of gasotransmitters and one gas is not perhaps in some way more important than another. This theory is conformity with the concept on Holistic Medicine. At present the theory and method of the gasotransmitters system has not been studied in the traditional Chinese medicine of gastrointestinal system. The mode of PK-PD will be used to explore the new relationship between the whole regulation system of NO/CO/H2S and the mechanism of intestinal mucosa injury of the active ingredients in Radix Aucklandiae. It will provide a new theory and method for traditional Chinese medicine on the protection of intestinal mucosa injury.

英文关键词： Intestinal mucosa injury;Radix Aucklandiae ;Sesquiterpenes;Gasotransmitters;PK-PD