威灵仙总皂苷调控肠道微生态-Treg/Th17细胞失衡抗免疫性炎症的作用机制研究

项目名称： 威灵仙总皂苷调控肠道微生态-Treg/Th17细胞失衡抗免疫性炎症的作用机制研究

项目编号： No.81473396

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘丽芳

作者单位： 中国药科大学

项目金额： 72万元

中文摘要： 自身免疫性疾病(AID)已成为严重影响人类健康的重大疾病之一。通过调控肠道微生态平衡来改善AID的疾病进程是近期提出的全新策略,但是这个新策略面临的主要障碍是：人们对肠道共生菌群的变化是如何影响自身免疫反应的机制并不十分清楚。威灵仙是我国传统的抗风湿中药，我们前期的研究已经证实威灵仙中的三萜皂苷类成分均具有显著的抗免疫性炎症活性，但该类物质在体内的生物利用度极低，现有的研究模式难以科学阐明其药效学作用机制，因此，本项目结合现代化学，微生物学，药理学,代谢组学及蛋白质组学等多学科手段和方法，充分考虑中药作用复杂性和整体性的特点，针对AID发生发展过程中肠道微生态-Treg/Th17细胞失衡这一重要事件，深入研究威灵仙总皂苷改善肠道菌群组成和代谢与调控肠道Treg/Th17细胞平衡的内在作用机制，为AID的防治和研究提供新的靶点，同时也为中药皂苷类成分的深入研究和合理应用提供新的思路和方法。

中文关键词： 威灵仙总皂苷；自身免疫病；肠道微生态；Treg/Th17细胞；作用机制

英文摘要： Autoimmune disease (AID) has become one of the critical diseases seriously influencing the human health. Currently, a new strategy has been proposed for the treatment of AID through regulation of gut microbiota homeostasis to slow the progression of AID. However, the mechanism of this regulation remains enigmatic. Clematidis Radix et Rhizoma (Wei-ling-xian) is a most commonly used Chinese herb with the effect of anti-rheumatism. Our previous work has confirmed that triterpenoid saponins are the main active components that responsible for its effect. However, the extremely low absolute bioavilability of these components in vivo become the main obstacle for further mechanism study. The disruption of Treg/Th17 cells balance of intestine is an important phenomenon in AID genesis and development, thus this study is focused on the effect of total saponins of Clematidis on improving the intestine gut microbiota composition and regulation of Treg/Th17 cells balance, and the mechanism involved. Furthermore, it is essential to consider the complexity and integrity of traditional Chinese medicine and use the multidisciplinary approach.This research will provide new targets and signal pathways for prevention and treatment of AID and drug development, also new ideas and approaches for further investigation and use of saponins from Chinese herb.

英文关键词： Total saponins of Clematidis;autoimmune disease;gut microbiota;Treg/Th17 cells;action mechanism