circAGFG1/miR-195-5p/PD-L1轴在脓毒症诱发急性肺损伤中的作用机制研究

脓毒症常伴随着急性肺损伤等并发症，具有高致死率和致残率。近年来，脓毒症诱发急性肺损伤患者呈显著上升趋势，但其发病机制仍不明确。课题组前期研究发现抑制miR-195-5p可以靶向上调细胞程序性死亡配体-1（PD-L1），并有效改善脓毒症诱发的急性肺损伤，而环状RNA（circAGFG1）可靶向抑制miR-195-5p。然而，circAGFG1/miR-195-5p/PD-L1轴在肺上皮细胞中的机制仍未阐明。据上提出假说：在脓毒症诱发的急性肺损伤中，上调circAGFG1抑制miR-195-5p进而靶向上调气道上皮细胞PD-L1水平，从而改善疾病症状。本课题拟结合细胞、分子生物学手段，从临床、细胞及动物水平深入阐明circAGFG1/miR-195-5p/PD-L1轴在脓毒症诱发急性肺损伤中的作用机制，为脓毒症诱发急性肺损伤诊断标志物、新疗法开发提供分子靶点及理论依据，具有重要的研究价值。

Sepsis is often accompanied by complications such as acute lung injury (ALI), have high mortality and disability. In recent years, the number of sepsis patients complicated by acute lung injury has increased significantly, but its pathogenesis is still unclear. Previous studies have found that inhibition of miR-195-5p can target up-regulation of Programmed Death Ligand 1(PD-L1) and effectively improve sepsis-induced acute lung injury, while circular RNA (circAGFG1) can target miR-195-5p. However, the mechanism of the circAGFG1/miR-195-5p/PD-L1 axis in airway epithelial cells is unclear. Therefore, we propose the hypothesis: "In the acute lung injury caused by sepsis, miR-195-5p can be inhibited by up-regulating circAGFG1, and then target up-regulation of PD-L1 expression in airway epithelial cells, thereby improving the mechanism of disease phenotype". Based on previous research, this project intends to combine cell and molecular biological methods to clarify the mechanism of circAGFG1/miR-195-5p/PD-L1 axis in sepsis-induced ALI from the clinical, cellular and animal levels. It can provide diagnostic markers for sepsis-induced ALI, and also provide new molecular targets and theoretical basis for the prevention and treatment of the disease, which has important research value.