基于MAPK与NF-κB信号通路的黄藤素抗急性肺损伤机制研究

项目名称： 基于MAPK与NF-κB信号通路的黄藤素抗急性肺损伤机制研究

项目编号： No.81460565

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张旋

作者单位： 昆明医科大学

项目金额： 46万元

中文摘要： 急性肺损伤起病急、进展快、预后差，病死率高，是临床常见危急重症，目前治疗措施及药物效果不理想，因此寻找急性肺损伤新的治疗靶点和有效防治药物是当前亟待解决的重要问题。黄藤素是我国自行研制的纯天然植物药，因其具有抗炎、抗病毒、抗菌、增强免疫等功效，被称为植物抗生素。我们前期初步研究发现，黄藤素能够明显降低脂多糖LPS致急性肺损伤小鼠死亡率，降低肺毛细血管通透性、减轻肺水肿、肺炎症反应和肺损伤程度，提示黄藤素对急性肺损伤的防治有很大的应用潜力。然而，黄藤素防治急性肺损伤的机制有待深入研究。本研究拟在前期研究发现基础上，进一步深入评价黄藤素防治急性肺损伤的作用，探讨黄藤素对急性肺损伤时MAPK和NF-κB信号通路中相关基因和microRNA的影响，从MAPK和NF-κB信号通路阐明黄藤素防治急性肺损伤的分子机制，为急性肺损伤的防治提供新的候选药物，为拓宽黄藤素的临床应用范围提供较好的科学依据。

中文关键词： 急性肺损伤；黄藤素；核因子-κB；微小RNA；MAPK

英文摘要： Acute lung injury is a common critical illness with sudden onset, rapid progress, poor prognosis and high mortality. The current therapeutic measures and drugs are not satisfying. Therefore, there is an urgent demand for finding new therapeutic targets and drugs for acute lung injury. Fibrauretin is a natural plant drug totally developed by our country, and is considered as a plant antibiotics as it has antiinflammatory, antiviral and antibacterial activities and immunopotentiating activity. In our previous work, we found that fibrauretin reduced the mortality of mice with acute lung injury induced by LPS, reduced the permiability of pulmonary capillaries, reduced the degree of pulmonary edma and inflammation, thus ameliorated acute lung injury. Our findings suggest that fibrauretin has good potential in prevention of acute lung injury. However, the mechanism of action of fibrauretin in prevention of acute lung injury still needs further study. In this project, we will further evaluate the effect of fibrauetin in prevention of acute lung injury, explore the effect of fibrauetin on the genes and microRNAs related to MAPK and NF-κB singnal pathway during acute lung injury, so as to clarify the molecular mechanism of fibrauetin in prevention of acute lung injury and provide new drug candidate for acute lung injury and lay good scientific foundation for broadening the clinical application of fibrauetin.

英文关键词： Acute lung injury;Fibrauretin;NF-κB;MicroRNA;MAPK