肠-肝轴：从MAFLD患者中分离的E.coli NF73-1作用于肠血管屏障对MAFLD进展的影响和机制研究

在肠道中，除肠道的生物、物理、化学和免疫屏障外，肠道和肝脏之间存在重要的“肠—血管”屏障。它做为肠道和肝脏之间的最后一道防线，其完整性更决定了肠道微生物能否移位至肝脏，造成肝脏损伤。而目前针对其功能和作用的研究极其匮乏。.在本课题组前期研究中，从MAFLD患者肠道中鉴定出丰度最高和致病性最强的大肠杆菌菌株 E. coli NF73-1（中国授权专利：201610591293.4），动物实验发现E. coli NF73-1可移位至MAFLD小鼠肝脏，激活肝脏巨噬细胞，在MAFLD疾病进展的炎性阶段发挥重要作用。预实验结果提示E. coli NF73-1可导致MAFLD小鼠肠道血管内皮细胞损伤特异性标记PV1的表达上调，本课题拟在此基础上，进一步探究肠道致病菌株E. coli NF73-1对“肠—血管”屏障的影响及其对肠血管内皮细胞的作用机制。

In the intestine, there is an important "gut-vascular" barrier between the intestine and the liver, besides the biological, physical, chemical and immune barriers. It is the last line of defense between the intestine and the liver, and its integrity determines whether the gut microbes can migrate to the liver and cause liver damage. At present, most studies have failed to focus on its function and effect..In previous studies, we named the most abundant and pathogenic E.coli NF73-1 (authorized patent in China: No. 201610591293.4) from the gut of MAFLD patient. .Translocation of E.coli NF73-1 into the liver led to an increase in hepatic M1 macrophages, causing triglyceride synthesis and inflammation in MAFLD mice. Preliminary experimental results suggest that E. coli NF73-1 can increase the expression of PV1(specific marker of damaged gut vascular endothelial cell) in MAFLD mice. On this basis, this project intends to further explore the role of E.coli NF73-1 on the "gut-vascular" barrier and its mechanism on MAFLD mice.