Roux-en Y胃旁路手术通过肠源性LPS诱导的肥大细胞外泌体缓解T2DM的机制研究

RYGB gastric bypass surgery can effectively alleviate type 2 diabetes mellitus (T2DM), but the specific mechanism is still unclear. Recent research shows that: endotoxin (LPS) is closely related with the occurrence and development of T2DM, LPS is mainly from cell wall of Gram negative bacteria (G-). Mast cells are involved in the diabetes process and MC-Exo plays a coordinating role in proinflammation and prophylaxis. Therefore, we suggest that the mechanism of RYGB gastric bypass remission of T2DM may be related to LPS-induced MC-Exo, MC -Exo may reduce pancreatic β-cell local inflammation, improve pancreatic β-cell function, reduce insulin resistance, and thus relieve T2DM. In this study, RYGB diabetes rats were studied by cell biology and molecular biology methods, we propose that the verification of LPS concentration in the blood decreased is one of the key mechanisms of RYGB operation to improve T2DM. At the same time we explore whether LPS regulated TLR4/MAPK/NF-κB pathway by inducing exosomes from mast cell for improving pancreatic cell function. This study aimed to explore the mechanism of type 2 diabetes on RYGB procedure,meanwhile this may provide new experimental evidence for developing new drugs based on intestinal microflora.

RYGB胃旁路术能有效缓解2型糖尿病（T2DM），但具体机制仍未阐明。新近研究表明：RYGB术后的T2DM大鼠血中内毒素（LPS）明显降低。肥大细胞参与糖尿病过程，并且肥大细胞外泌体（MC-Exo）又能在促炎及抑炎中发挥协调作用，因此我们提出可能的假设：RYGB胃旁路术缓解T2DM的机制可能与LPS诱导的MC-Exo相关，MC-Exo可能降低胰岛β细胞局部炎症，改善胰岛β细胞功能，降低胰岛素抵抗，进而缓解T2DM。本项目通过研究LPS与胰腺组织（胰岛细胞）低度炎症反应的相关性，验证“血中LPS浓度降低是RYGB手术改善T2DM的关键机制之一”的假设。同时探索LPS是否是通过诱导MC-Exo介导TLR4/MAPK/NF-κB通路调控胰腺组织炎症因子的表达，改善胰腺细胞功能的分子机制。该研究对于RYGB治疗2型糖尿病的机理及以肠道菌群为靶点的新药研究将提供新的实验依据。