南苜蓿总皂苷改善2型糖尿病大鼠糖代谢的作用机制

摘要

目的 探讨南苜蓿总皂苷(TSMP)对2型糖尿病(T2DM)大鼠糖代谢的作用及其可能的机制.方法 采用高脂加小剂量链脲佐菌素诱导T2DM大鼠模型,将大鼠分为对照组、模型组、二甲双胍组(0.2 g/kg)、TSMP高剂量组(1.4 g/kg)、TSMP低剂量组(0.7 g/kg),连续给药4周,末次给药后测定胰岛素抵抗指数(IRI)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、肝糖原、白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、游离脂肪酸(FFA)、瘦素(Leptin)水平,以及丙酮酸激酶(PK)、已糖激酶(HK)、葡萄糖-6-磷酸酶(G-6-Pase)、果糖-1,6-二磷酸酶、葡萄糖激酶(GK)的活性;检测肝脏组织中G-6-Pase、磷酸烯醇式丙酮酸羧激酶(PEPCK)蛋白的表达.结果 与模型组比较,给予高剂量(1.4 g/kg) TSMP能降低T2DM大鼠IRI、FBG、HbA1c、IL-1β、TNF-α、FFA、Leptin水平,升高肝糖原水平,提高PK、HK、GK的活性,降低G-6-Pase、果糖-1,6-二磷酸酶的活性,并下调肝脏组织中G-6-Pase、PEPCK蛋白表达水平,差异均有统计学意义(P＜0.05).结论 TSMP可以改善T2DM大鼠的糖代谢紊乱,可能与其促进葡萄糖的利用,减轻炎性反应和改善胰岛素抵抗有关.%Objective To explore the effect of total saponins from Medicago polymorpha (TSMP) on glucose metabolism in type 2 diabetes mellitus (T2DM) rats and its possible mechanism.Methods T2DM rats were established by feeding with fat diets and intraperitoneally injecting with STZ 30 mg/kg.The rats were divided into control group,model group,metformin group (0.2 g/kg),TSMP high dose group (1.4 g/kg) and TSMP low dose group (0.7 g/kg),which were administrated for four weeks.At the end of administration,blood samples were collected to determine insulin resistance index (IRI),levels of fasting blood glucose (FBG),glycosylated hemoglobin (HbAlc),hepatic glycogen,interleukin (IL)-1 β,tumor necrosis factor (TNF)-α,free fatty acids (FFA) and Leptin,and activities of pyruvate kinase (PK),hexokinase (HK),glucose-6-phosphatase (G-6-Pase),fructose-1,6-bisphosphatase and glucokinase (GK).Western blot was used to detect the expression levels of G-6-Pase and phosphoenolpyruvate carboxykinase (PEPCK) proteins.Results Compared withthe model group,high dose (1.4 g/kg) TSMP decreased IRI,levels of FBG,HbA1 c,IL-1β,TNF-α,FFA and Leptin,and activities of G-6-Pase and fructose-1,6-bisphosphatase in T2DM rats (P＜ 0.05),while increased level of hepatic glycogen,and activities of PK,HK and GK (P＜0.05).Moreover,high dose (1.4 g/kg) TSMP down-regulated expression levels of G-6-Pase and PEPCK protein in liver tissues.Conclusion Chronic administration of TSMP can improved glucose homeostasis in T2DM rats,which might be related to promoting utilization of glucose,and alleviating inflammatory and insulin resistance.