基于Keap1/Nrf2/ARE通路探讨辣蓼防治胃粘膜损伤的作用机制及物质基础

以辣蓼为主的方药，在临床防治急性胃炎，疗效确切。我们前期研究已确定辣蓼防治急性胃黏膜损伤（AGML）的有效部位，但其作用机制尚未明确。多项研究表明氧化应激反应在AGML的发生、发展中起重要作用，其中Keap1/Nrf2/ARE信号通路是最重要的内源性抗氧化通路，辣蓼防治AGML机制可能通过该信号途径。为此本项目拟在前期研究基础上，对有效部位的化学成分进行分离、制备与鉴定；体外检测细胞抗氧化酶活性、Nrf2mRNA及下游靶基因和蛋白的变化，优选活性强、作用机制基本清晰的组分；利用AGML动物模型测定生化指标、胃病理切片，评价其功效，检测胃组织Keap1、Nrf2及下游靶蛋白表达水平，从Keap1/Nrf2/ARE信号通路变化及它们之间的相互关系，探究辣蓼防治AGML的作用机制及物质基础，为辣蓼临床防治AGML提供理论依据，丰富以抗氧化为切入点的中医药防治AGML的科学内涵。

Formulars mainly composed of Polygonum hydropiper are widely used to treat acute gastritis in clinic, and has good curative effect on it. Our previous studies have shown that Polygonum hydropiper has significant effect on the prevention and treatment of AGML, and further determine the effective fractions, but its mechanism is still not clear for us. The oxidative stress plays an important role in the occurrence and development of AGML, the Keap1/Nrf2/ARE signaling pathway is the most important endogenous antioxidant pathway, the effect of Polygonum hydropiper on the prevention and treatment of AGML is definite, and its mechanism is likely to be through the Nrf2 signal pathway. Based on the research above, to carry out the following work: The separation, preparation and identification of the chemical components of the active site will been performed; the antioxidase activity, Nrf2mRNA and downstream target gene and protein changes were detected in vitro, the ingredient of strong activity and clear mechanism of action will preferred; To determine the biochemical indicator and pathological sections in AGML animal model to evaluate its efficacy and to detect the level of Keap1 and Nrf2 protein expression, the expression of Nrf2mRNA and its downstream target genes, in order to discuss the mechanism and material basis of Polygonum hydropiper against AGML from aspects of Keap1/Nrf2/ARE signaling pathway and provide theory basis for the use of Polygonum hydropiper in treatment of AGML in the hope of shedding light on TCM treatment of AGML from oxidative stress.