作为一线抗疟药，青蒿素类药物挽救了全球数百万人的生命。近年来随着对该类化合物的深入研究，其免疫抑制活性越来越受到关注。目前认为，血红素是青蒿素类药物发挥抗疟作用的关键分子，而游离型血红素也可通过多种作用机制引起组织和细胞的损伤，与多种疾病相关。我们前期研究发现，游离血红素的水平与狼疮动物模型的发病程度具有相关性，青蒿素类化合物马来酸蒿乙醚胺（自主研发的治疗狼疮的1类新药，进入临床试验）在狼疮动物的疗效作用机制与血红素密切相关。因此，我们推测游离血红素及调节其合成、降解的关键酶在狼疮发病机制中可能扮演着重要的角色。本项目将进一步确证血红素在狼疮动物及患者中的关键病理作用，围绕血红素探究青蒿素类化合物治疗狼疮的分子靶点及作用机制。本项目研究将有助于进一步了解狼疮疾病的发病机制，为药物干预提供可能的新靶点，也将为青蒿素类化合物治疗自身免疫疾病的研究提供新的证据和思路。

Artemisinin drugs, as first-line treatment of malaria, has saved millions of lives. Beyond antimalaria, artemisinin and its derivatives are also being investigated in autoimmune diseases. Heme is currently regarded both the activating agent and the target of artemisinin drugs for their antimalaria activity. While free heme play an important role in the pathogenesis of diseases like inflammation, sepsis and kidney injury. Our previous study demonstrated that the level of free heme correlated with disease severity in lupus mice. The pharmacological effect and mechanism of action of SM934, a novel artemisinin analog, related with heme. Thus we deduced heme may play key role in the pathophysiology of SLE. Bases on these results, further studies would be carried out to explore the underlying mechanism of free heme in lupus, and evaluate the potential value of heme as a biomarker in autoimmune disease. This project will push forward the frontiers of drug discovery. And the research of drug target and biomarker will also bring forth new ideas in drug discovery and development.