糖尿病合并脓毒症患者日益增多；肠损伤是脓毒症患者发生多器官功能不全和死亡的重要原因。预实验发现糖尿病合并脓毒症小鼠肠损伤较非糖尿病严重，脓毒症状更重，死亡率更高；肠组织LncRNA LXLOC_003839(我们命名为LncRNA-DSI)显著上调，伴随miR-377及SIRT1显著下调及促炎M1巨噬细胞的标志物增加。体外细胞实验沉默LncRNA-DSI后，miR-377和SIRT1上调，M1巨噬细胞向抗炎的M2型转化，与内毒素及巨噬细胞共培养的肠粘膜上皮损伤减轻。据此，提出“LncRNA-DSI/miR-377/SIRT1通路调控巨噬细胞极化介导糖尿病合并脓毒症肠损伤”的科学假设。本研究拟建立正常与db/db糖尿病小鼠脓毒症模型及CD11c-DRT转基因小鼠建立糖尿病模型剔除M1巨噬细胞后的脓毒症模型，结合体外细胞学研究，验证假设，为糖尿病合并脓毒症肠损伤的防治提供有效的靶标和实验依据。

Intestinal injury has become a major course of multiple organ dysfunction syndrome (MODS) and increased mortality in patients with diabetes and concomitant sepsis whose morbidity is rapidly increasing. Our preliminary study demonstrated that in mice with diabetes and concomitant sepsis the severities of intestinal injury and the symptoms of sepsis were significantly higher than those in non-diabetic mice, accompanied with higher mortality. We firstly identified that the level of a long noncoding RNA, LXLOC_003839 which we named as LncRNA-DSI was significantly overexpressed in the intestinal tissue of mice with diabetes and concomitant sepsis as compared to non-diabetic mice, which was accompanied by significant downregulation of miR-377 and SIRT1 and significant increase of the biomarkers of M1 type macrophages. In in vitro cell culture studies, LncRNA-DSI silence resulted in increases of miR-377 and SIRT1 expression which was accompanied by the increased transforming of M1 to M2 macrophages and alleviation of intestinal cell injury when co-cultured with the endotoxin and macrophages. We, thus, hypothesized that via miR-377-SIRT1 signaling regulates macrophage polarization-mediated intestinal injury in mice with diabetes and sepsis. We will establish sepsis models in non-diabetic and in db/db diabetic mice, and also in CD11c-DRT transgenic mice following the establishment of diabetes and the ensuing removal of M1 macrophages. The present study was designed to test the hypothesis in vivo and in vitro experiments in an effort to identify effective therapies for the treatment and prevention of intestinal injury in subjects with diabetes and sepsis.