丹参-红花配伍调控胰岛素信号通路改善小鼠胰岛素抵抗的作用机制研究

Compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos regulate insulin signaling pathway and alleviate insulin resistance in mice

胰岛素抵抗是指胰岛素调控外周靶器官代谢葡萄糖的能力降低,是2型糖尿病的关键起始病因。本论文将探讨丹参-红花配伍对胰岛素抵抗的调控作用及机制。采用高脂饲料喂养的方法建立胰岛素抵抗C56BL/6J小鼠模型,评价丹参-红花配伍预防性给药对胰岛素抵抗小鼠的能量摄取和体重、血浆甘油三酯、总胆固醇、胰岛素和葡萄糖水平、口服糖耐量测试(oral glucose tolerance test,OGTT)和胰岛素耐量测试(insulin tolerance test,ITT),以及对肝、心、肾和骨骼肌中胰岛素通路关键信号分子基因转录和蛋白表达水平的影响。动物福利和实验过程均遵循南京中医药大学动物伦理委员会的规定。结果显示,丹参-红花配伍显著改善胰岛素抵抗小鼠的能量摄取过量和体重增长过速,以及血浆甘油三酯和总胆固醇的异常增高,持续并显著改善胰岛素抵抗小鼠的高胰岛素血症。OGTT和ITT结果显示,丹参-红花配伍显著提高胰岛素抵抗小鼠对胰岛素的敏感性,增强对葡萄糖的代谢能力。胰岛素信号通路评价结果显示,胰岛素抵抗小鼠肝、心、肾和骨骼肌中代谢调控途径显著抑制,有丝分裂调控途径异常增强。丹参-红花配伍对胰岛素抵抗小鼠肝、心、肾和骨骼肌中胰岛素信号通路的稳态失衡具有不同程度的调控作用。丹参-红花配伍调控胰岛素信号通路,提高胰岛素抵抗小鼠代谢葡萄糖的能力,具有显著改善小鼠胰岛素抵抗的作用。

Insulin resistance refers to the impaired ability of insulin to regulate glucose metabolism in peripheral organs,which is considered to be the etiology of type 2 diabetes.This study aims to explore the mechanism of improving insulin resistance by compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos(DH).Insulin resistance was conducted on C56BL/6 J mice by treatment of high fat diet.The energy intake and body weight,plasma levels of triglycerides,total cholesterol,insulin and glucose,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT),as well as gene transcription and protein expression levels of insulin signaling pathway in liver,heart,kidney,and skeletal muscle of insulin resistance mice were evaluated.Animal experiments and welfare were performed in compliance with the guidelines of Animal Ethics Committee of Nanjing University of Chinese Medicine.The results showed that DH treatment significantly alleviated the excessive food intake and weight gain,and significantly decreased the levels of plasma triglycerides and total cholesterol,and constantly mitigated the hyperinsulinemia in insulin resistance mice.The results of OGTT and ITT suggested that DH treatment dramatically improved the response of insulin resistance mice to insulin stimulated glucose metabolism.Furthermore,the imbalance of metabolic arm and mitogenic arm of insulin signaling pathway in insulin resistance mice was normalized after DH treatment.DH treatment regulated insulin signaling pathway and improved the ability of glucose metabolism of insulin resistance mice.