脓毒症是导致患者死亡的前十名疾病，其针对性的治疗稀缺。血必净有效防治脓毒症及其诱导的器官衰竭，成为广大患者的福音。 然而其防治感染诱发的器官衰竭的机制模糊，药效物质基础不详，制约其临床应用。机体依赖一类干扰素信号通路防止念珠菌脓毒症及其诱导的肾衰竭。我们发现血必净有效防治白念珠菌诱导的真菌性脓毒症及其诱导的肾衰竭，增强机体免疫力，可能直接或间接调控一类干扰素信号通路防治真菌感染。因此，提出血必净调控先天免疫细胞中一类干扰素信号通路缓解真菌性脓毒症诱导的器官衰竭的假说。拟围绕一类干扰素受体敲除鼠 （IFNAR1 KO）动物模型，整合多组学技术，在整体动物，细胞和分子水平, 深入验证我们的假说, 并初步阐明血必净防止真菌性脓毒症免疫调节的物质基础。本项目的完成将深入阐明血必净防治感染诱导的器官衰竭的免疫调节机制，为其临床应用提供指导。为开发新一代抗脓毒症药物奠定理论和物质基础。

Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit (ICU). Fungal infections, especially those caused by pathogenic Candida species, frequently lead to sepsis. Our network pharmacology analysis predicted that Xuebijing (XBJ), a Chinese medicine injection approved by Food and Drug Administration of China to treat sepsis and septic shock, may prevent fungal infection. We found that XBJ rescued mice from lethal Candida sepsis in a disseminated C. albicans infection model and abolished colonization of C. albicans in kidneys. XBJ enhanced viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 at the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented colonization of C. albicans in kidneys, but also sustained survival of kidney epithelial cells partially by maintaining the expression of GRP78. Network pharmacology analysis predicted that XBJ regulates IFNα and upstream regulators of type I IFNs, TLR2, TLR3 and TLR4. These results were strengthened by literatures. We hypothesized that XBJ prevents Candida sepsis by regulating type I IFN pathway in innate immune cells. We plan to test our hypothesis in IFNAR1 knockout mice, human monocyte cell line THP-1, using cutting-edge technologies such as RNA-seq, Real-time PCR and cytokine arrays. We will also determine whether major compounds in XBJ can mimic the function of XBJ in regulating type I IFN pathway. This work will uncover the regulatory role of XBJ on innate immune system upon Candida infection and the material basis of XBJ in preventing Candida infection. It may shed light on developing the next generation of medicine for sepsis management.