蒙药沙蓬粗寡糖通过调控外泌体miRNA-155治疗“希和日西精病”引起的“通拉嘎未消化症”分子机制研究

IR、糖脂代谢紊乱和炎症在T2DM-NAFLD疾病中发挥重要作用，外泌体miRNA-155又是IR、糖脂代谢紊乱和炎症反应关键调节因素，故寻找安全有效的外泌体miRNA-155抑制剂是防治T2DM-NAFLD的关键因素之一。前期研究显示蒙药AOS可调节糖脂代谢、改善IR，抑制T2DM-NAFLD的进展，并发现AOS可调控外泌体miR-155水平。本研究拟用自发性肥胖db/db小鼠和3T3-L1细胞，用分子生物学、细胞免疫学和组织形态学等方法，观察AOS对外泌体miR-155分泌的影响及机制，并探讨外泌体miRNA-155与炎症、T2DM-NAFLD的关联性及AOS的干预作用；构建含外泌体miR-155巨噬细胞与肝细胞AML-12共培养体系，验证AOS通过调控外泌体miR-155分泌干预T2DM-NAFLD的发生、发展，揭示蒙药AOS治疗“希和日西精病”引起的“通拉嘎未消化症”的科学内涵。

Insulin resistance (IR), glucose and lipid metabolic disorder and inflammatory response play important roles in T2DM-NAFLD disease. And exosome miR-155 is a key regulator of IR, glucose and lipid metabolic disorder and inflammatory response. Therefore, finding a safe and effective miRNA-155 inhibitor is one of the key factors in the prevention and treatment of T2DM-NAFLD. Previous researches reported that AOS could regulate the glucose and lipid metabolism, improve IR and inhibit the development of T2DM-NAFLD. In addition, AOS could regulate the level of exosome miR-155. Based on these results, our project aims to demonstrate the effects and further mechanisms of exosome miRNA-155 using in spontaneously obese db/db mice and 3T3-L1 cell that treated with AOS by applying the molecular biology, cellular immunology and histomorphology methods, and to explore miRNA-155 and inflammation, T2DM-NAFLD correlation and AOS intervention; Besides, we aim to establish co-culture system of macrophages containing miRNA-155 and AML-12 liver cell to identify that treatment with AOS interferes with the occurrence and development of T2DM-NAFLD by regulating exosome miRNA-155 secretion. This project will reveal the scientific connotation of AOS in treatment of"Tonglaga undigestive disease" caused by "Xiherixijing Disease"