脓毒症是重症医学最为棘手的危重症之一，通常由感染引发，最常累及胃肠道，其机制复杂，目前尚不完全清楚，深入探讨脓毒症肠损伤的发生机制对于改善患者预后具有至关重要的临床意义。申请者前期研究发现，由Cx43组成的细胞缝隙连接（GJ）可以在细胞间传递“死亡信号”导致相邻细胞损伤不断放大，但其本质尚不明确。前期预实验显示，脓毒症肠组织中升高的miR-181b可通过GJ传递到相邻细胞；抑制miR-181b功能可以减轻脓毒症肠损伤。同时采用Targetscan软件分析预测miR-181b下游靶基因最有可能为Sirt1，可以调节FOXO3a的乙酰化状态，进而影响其下游相关凋亡靶基因表达。据此设想：脓毒症肠组织中，升高的miR-181b，通过Cx43组成的GJ传递到相邻的肠粘膜上皮细胞中，负调控Sirt1，对FOXO3a的去乙酰化作用减弱，发生核转位，与下游凋亡相关基因结合，促进细胞凋亡，导致肠道损伤。

Sepsis is one of the most serious diseases in critical care medicine. The disease develops rapidly and its mortality is very high. It is usually caused by infection, most often involving the gastrointestinal tract, and its mechanism is complex. Therefore, it is of great clinical significance to explore the mechanism of intestinal injury in sepsis to improve the prognosis of patients. Previous studies have found that Gap junction (GJ), composed of Connexin (Cx) protein, can transmit "death signal" between cells, resulting in the enlargement of adjacent cell damage, but the essence of "death signal" is not clear. The preliminary experiment results showed that the content of miR-181b in the intestinal tissue of sepsis increased significantly, and it could be transmitted to adjacent cells through GJ, while inhibiting miR-181b function could reduce the intestinal injury of sepsis. At the same time, Targetscan software was used to predict the most likely target gene for the downstream target of miR-181b to be Sirt1. As a deacetylase, Sirt1 affects the expression of the downstream related apoptosis target gene by regulating the acetylation status of FOXO3a. We hypothesize that in sepsis with intestinal injury, miR-181b increased significantly, which could be transmitted to the neighboring intestinal epithelial cells through GJ composed of Cx43, negatively regulated Sirt1 gene. The downregulation of Sirt1 resulted in the diminishment the deacetylation ability FOXO3a. Then, FOXO3a entered the nucleus and combined with apoptosis related genes, which promoted cell apoptosis and intestinal injury.