辣木叶多糖对STZ诱导糖尿病小鼠的降糖效果及其机制

Hypoglycemic Effect of Moringa oleifera Leaf Polysaccharide on STZ-induced Diabetic Mice and Its Mechanism

为探讨辣木叶多糖(Moringa oleifera leaf polysaccharide,MOLP)对糖尿病小鼠的降糖效果及其机制,通过建立链脲佐菌素(Streptozotocin,STZ)诱导糖尿病小鼠模型,将实验小鼠设为正常空白组、模型组、MOLP低剂量组(100 mg/kg·bw)、中剂量组(200 mg/kg·bw)、高剂量组(400 mg/kg·bw)和阳性药物组(盐酸二甲双胍200 mg/kg·bw),每组8只,灌胃28 d,测定空腹血糖、血清糖化蛋白、血清胰岛素、肝/肌糖原等生化指标,对肝脏和胰腺中糖代谢关键基因(肝X受体(Liver X Receptor,LXR)、胰腺十二指肠同源异形盒1(Pancreatic duodenal homeobox-1,PDX-1)、葡萄糖激酶(Glucoskinase,GK)、磷酸烯醇丙酮酸羧激酶(Phosphoenolpyruvate carboxykinase,PEPCK)、葡萄糖6磷酸酶(Glucose-6-phosphatase,G6Pase)、葡萄糖转运载体2(Glucose transporter type 2,GLUT2)、胰岛素受体底物1/2(Insulin receptor 1/2,IRS1/2))进行测定,并对各组小鼠肝脏和胰腺组织进行HE染色,观察其组织形态。结果表明:MOLP降糖效果显著,且呈现一定的量效反应关系,MOLP高剂量组(400 mg/kg·bw)的血糖降低水平最为接近阳性药物组,其相关机制为表达显著上调的LXR和PDX-1通过调控其下游基因PEPCK、G6Pase、GK、GLUT2和IRS1/2 mRNA表达,从而改善糖尿病小鼠的糖代谢紊乱,使其损伤的肝脏组织和胰腺组织得到有效改善,血清胰岛素和肝糖原含量增加,最终达到降血糖作用。

To explore the hypoglycemic effect of Moringa oleifera leaf polysaccharide(MOLP)on diabetic mice and its corresponding mechanism,a streptozotocin(STZ)-induced diabetic mouse was modeled.The mice were then divided into groups exposed to low(100 mg/kg·bw),medium(200 mg/kg·bw),and high dosage(400 mg/kg·bw)of MOLP,with a normal blank group,model group and a positive drug group(hydrochloric acid dimethylbiguanide,200 mg/kg·bw).Eight mice in each group were gavaged for 28 d.Fasting blood glucose,serum glycated protein,serum insulin,hepatic/myocardial glycogen and other biochemical indexes were determined.Additionally,the key genes of glucose metabolism,including liver X receptor(LXR),pancreatic-duodenal homeobox-1(PDX-1),glucokinase(GK),phosphoenolpyruvate carboxykinase(PEPCK),glucose 6-phosphatase(G6Pase),glucose transporter type 2(GLUT2)and insulin receptor substrate 1/2(IRS1/2)were measured in the liver and the pancreas.Furthermore,the mice's liver and pancreas tissues in each group were stained with HE to observe their histomorphology.The results showed that MOLP exhibited a significant hypoglycemic effect and a dose-response relationship.The level of blood glucose reduction in the MOLP high-dose group(400 mg/kg·bw)was closest to that of the positive drug group.The underlying mechanism was that the significantly upregulated expression of LXR and PDX-1 ameliorated the glucose metabolism disorders in diabetic mice by regulating the expression of their downstream genes including PEPCK,G6Pase,GK,GLUT2 and IRS1/2 mRNA.This regulation facilitated the improvement of the damaged liver and pancreatic tissues,increased serum insulin and hepatic glycogen content and ultimately resulted in a hypoglycemic effect.