探索“脾主为卫”环节对糖脂代谢稳态的调节机制

Explore Regulation Mechanism of “The Spleen for Defend” on Homeostasis of Glucose and Fat Metabolism

目的:运用益气活血法探索“脾主为卫”环节调节糖脂代谢紊乱的潜在分子机制。方法:采用Western Blot法研究金芪降糖方对KKAy小鼠肝脏和肌肉中PI3K/AKT信号通路的影响;观察金芪降糖方在体外对HepG2细胞TG蓄积的作用和机制。结果表明:金芪降糖方明显上调KKAy小鼠骨骼肌内PI3K、p-PI3K、AKT、p-AKT蛋白的表达;金芪降糖方及其组分均具有降低HepG2细胞TG蓄积的作用,且具有明显的量效关系;应用分别加入抑制剂或激动剂的方法后,其抑制作用依然存在,但抑制作用明显降低,表明金芪降糖方抑制TG蓄积可能与激活PI3K/AKT和AMPK信号通路有关。结论:“脾主为卫”环节通过促进机体胰岛微循环从而发挥其改善糖脂代谢紊乱的作用,其机制可能与同时干预多条通路以调节疾病状态下失衡的代谢网络相关。

Objective: To analyze the molecular biological mechanism of “The Spleen for Defend” regulating glucose and lipid metabolism disorder. Method: The effects of “Jinqi jiangtang” formula on the PI3K/AKT pathway in the liver and muscle of KKAy mice were studied by Western Blot. HepG2 cells were induced by sodium oleate to build lipid accumulation model. Inhibitors such as Com-pound C (AMPK inhibitor), STO-609 (CaMKK inhibitor), Oxtromorine (acetylcholine receptor inhibitors), Cytochalasin B (GLUT4 inhibitors), and agonist IGF-1 (PI3K agonist) were used to explore possible mechanism of lipid regulation. It is suggested that possible mechanism on TG accumulation of “Jinqi jiangtang” formula could inhibit TG accumulation through activating AMPK and PI3K/AKT signaling pathway. Conclusion: The effects of “The Spleen for Defend” on the improvement of the disturbance in the lipid and glucose metabolism may be achieved by promoting islet microcirculation, and its mechanism may be related to intervention of multiple pathways to regulate the unbalanced metabolic network in the state of disease.