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目的:研究番石榴叶总黄酮对糖尿病小鼠肝脏葡萄糖代谢及胰岛素信号通路相关分子表达的影响,探索其降糖作用机制。方法:雄性BALB/c小鼠,腹腔注射链脲佐菌素(streptozocin,STZ)60 mg·kg-1连续5 d后,血糖仪检测空腹血糖水平,以连续3 d空腹血糖浓度>11.1 mmol·L-1为糖尿病模型成功标准。糖尿病小鼠随机分为模型组和番石榴叶总黄酮低、中、高剂量治疗组,每组10只,另设10只正常小鼠。低、中、高剂量治疗组分别以番石榴叶总黄酮0.093,0.186,0.372 g·kg-1灌胃,正常组和模型组以等体积蒸馏水灌胃,2周后测其空腹血糖、病理观察胰岛数目及形态学改变、荧光PCR法检测肝葡萄糖激酶(glucokinase,GK),葡萄糖激酶调节蛋白(glucokinase regulatory protein,GKRP),葡萄糖转运蛋白-2(glucose transporter 2,GLUT-2),胰岛素生长因子-1(insulin growth factor-1,IGF-1),胰岛素受体底物-1(insulin receptor substrate-1,IRS-1),胰岛素受体底物-2(insulin receptor substrate-2,IRS-2)表达。结果:与正常组比,模型组小鼠体重明显降低(P<0.01),血糖明显升高(P<0.01);胰岛变性明显,胰岛数目明显减少、体积变小、甚至消失;肝GK,GLUT2,IGF-1,IRS-1和IRS-2表达下降,GKRP表达增高。与模型组比,番石榴叶总黄酮治疗组血糖明显降低(P<0.05),胰岛数目明显增多;GK,GLUT2,IGF-1,IRS-1和IRS-2表达升高,GKRP表达下降,中剂量组治疗效果最好(P<0.05)。结论:番石榴叶总黄酮低、中、高剂量均能明显降低STZ糖尿病小鼠血糖水平,可能与其增强肝脏GK,GLUT2,IGF-1,IRS-1,IRS-1表达,降低肝GKRP表达及促进胰岛再生有关。
Objective: To study the effect of total flavonoids from guava leaves on hepatic glucose metabolism and insulin signaling pathway-related molecules expression in diabetic mice and to explore its hypoglycemic mechanism. Methods: The male BALB / c mice were injected intraperitoneally with streptozocin (STZ) 60 mg · kg-1 for 5 days. The fasting blood glucose was measured by blood glucose meter and the fasting blood glucose concentration was 11.1 mmol · L-1 is the successful model of diabetes model. Diabetic mice were randomly divided into model group and low, medium and high dose guava leaf total flavonoids treatment group, with 10 mice in each group and 10 normal mice. The low, medium and high dose treatment groups were fed with the total flavonoids of Guava leaves 0.093,0.186 and 0.372 g · kg-1 respectively. The normal group and model group were given gavage with equal volume of distilled water, and the fasting blood glucose was measured after 2 weeks. The numbers and morphological changes of islets were detected by enzyme linked immunosorbent assay (ELISA). The expression of glucokinase (GK), glucokinase regulatory protein (GKRP), glucose transporter 2 (GLUT-2), insulin growth factor (IGF-1), insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2) )expression. Results: Compared with the normal group, the body weight of the model group was significantly lower (P <0.01) and the blood glucose was significantly higher (P <0.01). The islet degeneration was obvious, the number of islets was significantly reduced and the volume was smaller or even disappeared. , IGF-1, IRS-1 and IRS-2 expression decreased, GKRP expression increased. Compared with model group, the content of GK, GLUT2, IGF-1, IRS-1 and IRS-2 were significantly increased and the expression of GKRP was decreased in the treatment group of guava leaf total flavonoids (P <0.05) The best dose group (P <0.05). CONCLUSION: Low, medium and high doses of total flavonoids from guava leaves can significantly reduce the blood glucose level in STZ diabetic mice, which may be related to its enhanced expression of GK, GLUT2, IGF-1, IRS-1 and IRS- Promote islet regeneration related.