创伤脓毒症具有高发生率和死亡率，发病机制复杂。lncRNA MIR3945HG是申请人筛选并命名的参与脓毒症发生的长链非编码RNA分子，前期研究发现lncRNA MIR3945HG调节创伤脓毒症炎症反应程度，但具体的分子机制尚不清楚。本项目拟从体内外细胞和分子水平系统阐述lncRNA MIR3945HG在创伤脓毒症中的作用及分子机制，通过染色体免疫共沉淀和可接近性实验等技术阐明lncRNA MIR3945HG自身表达的调控机制；通过RIP、RNA pull-down等技术锁定lncRNA MIR3945HG调控的靶分子及信号通路，通过药物和基因编辑手段阻断或激活lncRNA MIR3945HG调控靶分子，观察lncRNA MIR3945HG敲除或过表达引起的炎症反应逆转程度。为扩展创伤脓毒症发生机制和干预靶点提供新思路和实验线索。

Traumatic sepsis has high incidence and mortality, and its pathogenesis is complex. LncRNA MIR3945HG (ENSG00000251230.1), a novel long non-coding RNA discovered and annotated by the applicant, is closely related to sepsis. Previous studies have found that lncRNA MIR3945HG participates in the regulation of inflammatory response of traumatic sepsis, however, the role of lncRNA MIR3945HG in the traumatic sepsis remains unclear. This project aims to clarify the role and mechanism of lncRNA MIR3945HG in traumatic sepsis at the cellular and molecular level. Using chromosome immunoprecipitation and accessibility experiments to elucidate the regulatory mechanism of lncRNA MIR3945HG self-expression, and using RIP and RNA pull-down to lock the target molecules and signaling pathways of lncRNA MIR3945HG regulation, respectively. We will block or activate the key downstream factor regulated by lncRNA MIR3945HG via drug and genetic editing to reverse the phenotypes of lncRNA MIR3945HG knockout or transgenic experiments. The findings in this study will clarify the role and mechanism of lncRNA MIR3945HG in traumatic sepsis, and will provide novel ideas and experimental clues for exploring intervention targets for prevention and treatment of traumatic sepsis in the future.