薯蓣粥对2型糖尿病模型大鼠糖代谢及胰岛功能的影响

Effects of Shuyu Gruel(薯蓣粥) on the Glucose Metabolism and Islet Function of Type 2 Diabetic Model Rats

目的探讨薯蓣粥改善2型糖尿病糖代谢和胰岛素抵抗的可能作用机制。方法50只雄性Wistar大鼠随机分为空白组8只和造模组42只。造模组给予高脂高糖饲料喂养6周后结合腹腔注射链脲佐菌素(STZ)建立2型糖尿病大鼠模型。造模成功的32只大鼠随机分为模型组、薯蓣粥组、二甲双胍组、联合用药组,每组8只。薯蓣粥组给予薯蓣粥灌胃,其中山药含量12 g/(kg·d),二甲双胍组给予盐酸二甲双胍片100 mg/(kg·d)灌胃,联合用药组上午给予薯蓣粥,下午给予盐酸二甲双胍片灌胃(剂量同上),空白组、模型组给予10 ml/(kg·d)生理盐水灌胃,持续干预6周。检测干预前及干预第2、4、6周各组大鼠空腹血糖(FBG)水平,干预6周后各组大鼠进行口服葡萄糖耐量试验(OGTT),计算曲线下面积(AUC)、血清空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR),检测大鼠骨骼肌单磷酸腺苷酸激活蛋白激酶(AMPK)、葡萄糖转运蛋白4(GLUT-4)mRNA表达,骨骼肌AMPK、磷酸化单磷酸腺苷酸激活蛋白激酶(p-AMPK)、GLUT-4蛋白水平。结果与模型组比较,薯蓣粥组、二甲双胍组、联合用药组干预2、4、6周AUC、FINS、HOMA-IR及干预第4、6周FBG水平均降低,p-AMPK/AMPK,GLUT-4蛋白及mRNA表达显著增加(P<0.05)。与薯蓣粥组比较,联合用药组AUC、FINS、HOMA-IR降低,GLUT-4蛋白及mRNA、AMPK mRNA表达升高,干预第4周、第6周FBG水平显著降低(P<0.05)。薯蓣粥组大鼠FBG水平从干预第2周开始至第6周逐渐降低(P<0.05);二甲双胍组和联合用药组大鼠FBG水平从干预前至第6周逐渐降低(P<0.05)。在OGTT试验中,模型组的血糖水平未见明显回落,薯蓣粥组、二甲双胍组、联合用药组在0.5 h时血糖出现高峰,1 h时开始明显下降。结论薯蓣粥能够改善2型糖尿病模型大鼠的糖代谢及胰岛素功能,且与二甲双胍联用效果更佳,其作用机制可能与调节骨骼肌的AMPK通路相关。

Objective To explore the mechanism of Shuyu Gruel(薯蓣粥,SY)in improving glucose metabolism and insulin resistance in type 2 diabetes(T2D)model rats.Methods Fifty male Wistar rats were randomised into blank group(n=8)and modeling group(n=42).The rats in the modeling group were fed with high-fat high-sugar diet for six weeks and then were given intraperitoneal injection of streptozotocin(STZ)to establish T2D rat model.The successfully modeled 32 rats were randomly divided into model group,SY group,metformin(MET)group and combination group,with eight rats in each group.SY containing 12 g/(kg·d)of Shanyao(Rhizoma Dioscoreae)was given to the SY group by gavage;metformin hydrochloride tablets at the dose of 100 mg/(kg·d)was administered by gavage in the MET group;SY was taken in the morning and metformin hydrochloride tablets were given in the afternoon to the rats in the combination group in the same administration way with SY and MET group;10 ml/(kg·d)of normal saline was administered by gavage in the blank group and model group;all the interventions lasted for six weeks.Fasting blood glucose(FBG)was assessed before treatment and week 2,4 and 6 after treatment;the area under the curve(AUC)of oral glucose tolerance test(OGTT),fasting insulin in the serum(FINS),and insulin resistance index(HOMA-IR)were assessed;the mRNA expression of adenosine 5’-monophosphate-activated protein kinase(AMPK)and glucose transporter 4(GLUT-4),as well as the protein levels of AMPK,phosphorylated AMP-activated protein kinase(p-AMPK)and GLUT-4 in skeletal muscle were detected.ResultsCompared to those of the model group,AUC,FINS and HOMA-IR of the SY,MET and combination groups at week 2,4 and 6,as well as FBG level at week 4 and 6 significantly decreased,while the protein and mRNA expression of p-AMPK/AMPK and GLUT-4 significantly increased(P<0.05).Compared to SY group,the combination group had lower AUC,FINS and HOMA-IR,and higher GLUT-4 protein and mRNA expression and AMPK mRNA expression;and the FBG level at week 4 and 6 significantly decreased(P<0.05).The FBG level of SY group gradually decreased from week 2 to week 6(P<0.05),while that of MET group and combination group decreased from before to after 6 weeks of treatment(P<0.05).The OGTT showed that the glucose level of the model group did not drop significantly,and that of SY group,MET group and combination group peaked at 0.5 h and began to decrease significantly at 1 h.Conclusions SY could improve glucose metabolism and insulin resistance in T2D model rats,which may be related to the regualtion of AMPK pathway in skeletal muscle.To some extent,better effect can be achieved when SY is used in combination with metformin.