非甾体抗炎药（NSAIDs）引起的胃溃疡是临床常见不良反应。申请人关注中药与NSAIDs联用对其不良反应的改善作用，前期研究证实高良姜乙醇提取物（AOE）可降低阿司匹林所致小鼠胃溃疡指数，减轻黏膜损伤，抑制炎症因子释放，确切机制需要阐明。本申请聚焦于AOE对NSAIDs引起溃疡性胃损伤保护作用的机理研究。针对NSAIDs所致胃溃疡病理表现，本项目拟借助RT-PCR等分子生物学技术，评价模型组、AOE及其主要成分组COX、iNOS、cNOS、CSE和ECE-1等信号通路中关键蛋白的mRNA及蛋白表达的变化；通过胃壁细胞培养等评价对胃酸分泌的影响；通过胃部微气球植入法观察胃部过度活动的变化；利用LC-MS/MS技术研究AOE等对NSAIDs及主要代谢物系统暴露和处置过程的影响。本课题从不同角度、多个层面阐明高良姜改善NSAIDs所致大鼠溃疡性胃损伤的作用机理，为高良姜创新发展和应用提供依据。

Gastric ulcer caused by non-steroidal anti-inflammatory drugs (NSAIDs) is common drug adverse reaction. Recent years, we focused on relieving NSAIDs-induced gastric damage through co-administration of Chinese medicine and NDAIDs. Our preliminary results revealed that the ethanol extract of rhizome from Alpinia officinarum Hance (AOE) could reduce ulcer index, gastric mucosa damage induced by aspirin. AOE also inhibited inflammatory factor and up-regulated the prostaglandin E2. However, the underlying protection mechanisms of AOE from NSAIDs-induced gastropathy remain largely unknown. This application aims to investigate the mechanisms of AOE and its main active components which reduce the gastric damage in murine models according to the pathological mechanisms caused by NSAIDs, including aspirin, celecoxib, naproxen and indometacin. The current application will investigate the influence of AOE and its main components on COX, iNOS, cNOS, CSE and ECE-1 using RT-PCR and Western blotting, which are mediators of gastric ulcer and inflammation. The effects of AOE and its main components on NSAIDs-stimulated gastric acid secretion in isolated rat gastric mucosal cells are planned to investigate in this project. Also, the importance of gastric hypermotility in the pathogenesis of NSAIDs-induced gastric lesions in conscious rats will be studied using a miniature balloon which is inserted into the greater curvature of the forestomach. Meanwhile, the concentration of NSAIDs and their main metabolites in various biomatrix samples (e.g., plasma, bile, urine and feces) from model rats after oral dosing will be analyzed using ESI-interfaced LC-MS/MS methods. The methods will be used to evaluate the influence of AOE and its main components on the systemic exposure to and pharmacokinetic behaviors of NSAIDs and main metabolites after co-administration to model rats. This application plans to study the roles of Alpinia officinarum Hance from a new perspective and to elucidate the underlying mechanisms. The investigation of Alpinia officinarum Hance, which is capable of reducing gastric damage caused by NSAIDs, could be useful for clinical use for the potential management of complicated adverse reactions of NSAIDs.