中文摘要
AMPK信号通路在肥胖2型糖尿病的病理生理中至关重要。AMPK通路受损导致的糖脂代谢紊乱与肥胖2型糖尿病痰瘀互结证有共同的病因与病理性质。前期研究表明,痰瘀同治法有降糖、降脂、抗氧化、抗炎、保护血管内皮功能的作用。我们推测痰瘀同治法干预肥胖2型糖尿病的机制是通过调控AMPK通路来介导的。为了证实这一假说,本课题将以体外肥胖2型糖尿病肝细胞模型和自发性肥胖2型糖尿病模型鼠为研究对象,以AMPK通路为切入点,观察痰瘀同治法对AMPK信号通路及相关因子AMPK、LKB1、APN、LEP、AMP/ATP比值、 HMGR、PPARγ、GluT4、ACC、CPT-1、CS、PEPCK、PEK等指标的影响,以探索痰瘀同治法干预肥胖2型糖尿病糖脂代谢的靶点。本课题可望揭示痰瘀同治法改善肥胖2型糖尿病糖脂代谢的机制,为肥胖2型糖尿病防治提供新的思路和药物作用新靶点,具有重要的意义和价值。
英文摘要
AMPK pathway is very important in the pathophysiology of obese type two diabetes mellitus(T2DM).Both glycolipid metabolism disorders caused by AMPK pathway damage and phlegm and blood stasis in obese type two diabetes mellitus have a common etiology and pathological nature.Pre-research confirmed, the method of Tanyu Tongzhi has hypoglycemic, lipid-lowering, anti-oxidation, anti-inflammatory and protecting vascular endothelial function. we speculated that the mechanism of the method of Tanyu Tongzhi in obesity type 2 diabetes is achieved through regulating AMPK pathway.To test this hypothesis, this topic will use vitro obese type 2 diabetes hepatocyte model and spontaneous obese type 2 diabetic mice as research subjects, use AMPK pathway as an entry point to observe the influence on the index of AMPK,LKB1,APN,LEP,The ratio of AMP/ATP,HMGR,PPARγ,GluT4,ACC,CPT-1,CS,PEPCK,PEK by the method of Tanyu Tongzhi , to explore the intervention and targets by the method of Tanyu Tongzhi in obese type 2 diabetes. This research is expected to reveal the mechanism of the method of Tanyu Tongzhi improving glycolipid metabolism in obese type 2 diabetes,which can provide new ideas and new target of new drugs for obese type 2 diabetes and has great significance and value. .
结题摘要
AMPK信号通路在肥胖2型糖尿病的病理生理中至关重要。AMPK通路受损导致的糖脂代谢紊乱与肥胖2型糖尿病痰瘀互结证有共同的病因与病理性质。前期研究表明,痰瘀同治法有降糖、降脂、抗氧化、抗炎、保护血管内皮功能的作用。本课题将以体外肥胖2型糖尿病肝细胞模型和自发性肥胖2型糖尿病模型鼠为研究对象,以AMPK通路为切入点,观察痰瘀同治法对AMPK信号通路及上下游分子等指标的影响,以探索痰瘀同治法干预肥胖2型糖尿病糖脂代谢的靶点。动物实验及细胞实验结果表明丹瓜方可显著降低FBG、糖化血红蛋白水平(P<0.01),降低TC、TG水平(P<0.01),改善肝细胞脂滴的大小和数量,改善胰岛素敏感指数(P<0.05),增加GLU4含量(P<0.05),增加CPT-1含量(P<0.01),降低HMGR含量及mRNA表达水平(P<0.05),升高PPAR-Y含量及蛋白表达水平(P<0.05),升高AMPKα蛋白及其mRNA表达(P<0.01),提高上游APN蛋白、LKB1蛋白及其mRNA、LEPmRNA表达水平(P<0.01,P<0.05,P<0.05);提高AMPKα通路下游分子GLUT4、CPT1及PPARγ蛋白表达(P<0.05,P<0.01,P<0.05),降低AMPKα通路下游分子ACC蛋白及其mRNA表达水平(P<0.05),提高P-ACC蛋白表达水平(P<0.05)。结论:丹瓜方具有确切的降糖、降脂功效,与既往实验结果一致。丹瓜方改善糖脂代谢与调控AMPK信号通路有关。
