青蒿对湿热证疟疾小鼠的多靶点干预作用

疟疾是一种严重危害人类生命健康的传染病。现全球疟疾消除停滞不前，青蒿素复方治疟失败病例逐年增加，各类抗疟药物的抗性虫株迅速在世范围内蔓延，对全球的疟疾防治和消除形成巨大威胁。黄花蒿入药，清热、解暑、截疟、凉血，广泛分布于世界各地，包括欧洲中东部和亚洲北部，以及地中海、北非、亚洲南部及西南部各国，亦可适种于湿热疟区。现代临床研究证实青蒿干枝叶泡水，治疟效果高于或等于青蒿素复方。从古至今，青蒿抗疟效果佳，能有效防止药物抗性产生。但青蒿素抗疟机理尚不明确，青蒿素原药激活、靶标都不确定。故本研究拟利用生物信息技术，探索青蒿治疗湿热疟疾的多成分、多靶点、多通路的潜在作用机制，并进行动物实验验证；同时体外培育青蒿素、哌喹鼠疟抗性株，进行全基因分析，探索青蒿素抗性产生机制。该研究将加深对青蒿素和青蒿中药的认识，对指导合理用药、提高临床疗效、防止抗药株的产生、发现新的抗疟药物都具有重要意义。

Malaria is an infectious disease seriously endangering human life and health. Today, global malaria elimination remains stagnant, the number of malaria cases failing to respond to artemisinin-based therapy keeps increasing every year, and drug-resistant malaria strains are spreading rapidly around the world posing a great threat to malaria control and elimination efforts globally. Artemisia annua Linn clears away heat, relieves summer heat, treats malaria and cools blood. It is widely distributed throughout the world, including central and eastern Europe, northern Asia, as well as countries in the Mediterranean Sea, North Africa, and southern and southwestern Asia. It can also grow in hot and humid malarious areas. Modern clinical studies confirmed that the malaria treatment effect of dried branches and leaves of Artemisia annua soaked into water is higher than or equal to that of an Artemisinin compound. Since ancient times, Artemisia annua is efficient to treat malaria; it can effectively prevent drug resistance. However, the antimalaria mechanism of Artemisia annua is not clear, and the activation and target of Artemisinin are uncertain. Therefore, this study intends to use bioinformation technology to explore the potential mechanism of the multi-component, multi-target and multi-pathway action of Artemisia annua in the treatment of damp-heat malaria, and to carry out animal experiments to verify the above mechanism. In the meantime, the resistant strains to Artemisinin-Piperaquine are cultivated in vitro to complete genetic analysis in order to explore the resistance mechanism to Artemisinin. This study will deepen the understanding on Artemisinin and Artemisia Annua which will be of great significance in providing guidance for rational use of drugs, improving clinical efficacy, preventing the emergence of drug-resistant strains and discovering new antimalarial drugs.