Sepsis is recognized as the acute systemic inflammatory response to severe infection. It is main cause of multiple organ system dysfunction and even organ failure. Long non-coding RNA X inactivate-specific transcript (XIST) is implicated in multiple inflammatory diseases. The aim of present work was to investigate the precise mechanism of XIST underlying sepsis-induced acute liver injury. Rats were underwent cecal ligation and puncture (CLP) to establish sepsis-induced the animal models of acute liver injury. Hematoxylin and eosin (H&E) staining was performed to observe pathological alterations. Corresponding commercial assay kits were employed to analyze the levels of inflammatory cytokines and oxidative stress. Western blot and reverse transcriptional quantitative PCR (RT-qPCR) were performed to determine the expression of proteins and target genes. Finally, TUNEL and CCK-8 assays were performed to test apoptosis rate and cell viability, respectively. In our study, XIST and BRD4 were highly expressed in serum of patients with sepsis-induced acute liver injury. XIST knockdown ameliorated sepsis-induced acute liver injury and inhibited inflammation, oxidative stress, and cell apoptosis in sepsis-induced acute liver injury rats. Interestingly, XIST knockdown downregulated the expression of BRD4, and BRD4 overexpression abolished the impacts of XIST knockdown on inflammation, oxidative stress, and apoptosis of that LPS-induced Kupffer cells. We conclude that lncRNA XIST silencing protects against sepsis-induced acute liver injury via inhibition of the BRD4 expression. Therefore, XIST may be a biomarker for sepsis diagnosis and treatment.

脓毒症被认为是对严重感染的急性全身炎症反应。它是多器官系统功能障碍甚至器官衰竭的主要原因。长链非编码 RNA X 灭活特异性转录本 (XIST) 与多种炎症疾病有关。目前工作的目的是研究 XIST 导致败血症引起的急性肝损伤的确切机制。对大鼠进行盲肠结扎穿刺（CLP），建立脓毒症诱导的急性肝损伤动物模型。进行苏木精和伊红（H＆E）染色以观察病理改变。使用相应的商业化验试剂盒来分析炎性细胞因子和氧化应激的水平。进行蛋白质印迹和逆转录定量 PCR (RT-qPCR) 以确定蛋白质和靶基因的表达。最后，分别进行 TUNEL 和 CCK-8 测定以测试细胞凋亡率和细胞活力。在我们的研究中，XIST 和 BRD4 在脓毒症所致急性肝损伤患者的血清中高表达。XIST 敲低改善了脓毒症诱导的急性肝损伤，并抑制了脓毒症诱导的急性肝损伤大鼠的炎症、氧化应激和细胞凋亡。有趣的是，XIST 敲低下调了 BRD4 的表达，BRD4 过表达消除了 XIST 敲低对 LPS 诱导的 Kupffer 细胞炎症、氧化应激和凋亡的影响。我们得出结论，lncRNA XIST 沉默通过抑制 BRD4 表达来防止败血症诱导的急性肝损伤。因此，XIST可能是脓毒症诊断和治疗的生物标志物。