阿卡波糖调节2型糖尿病大鼠肠道SGLT1表达的影响

Influence of acarbose on expression of intestinal SGLT1 in rats with type 2 diabetes mellitus

目的探讨2型糖尿病大鼠模型的建模方法,对比阿卡波糖(拜唐苹)与格列美脲调节2型糖尿病大鼠的血糖水平,探讨阿卡波糖对2型糖尿病大鼠肠道钠-葡萄糖协同转运蛋白1(SGLT1)表达的影响。方法将40只SD雄性大鼠随机分为5组:正常对照组、正常对照+拜唐苹干预组、2型糖尿病模型对照组、糖尿病模型+拜唐苹干预组和糖尿病模型+格列美脲干预组,每组8只。糖尿病组的大鼠均给予高脂乳剂灌胃和高糖饮水,连续灌胃4周后,模型组大鼠一次性腹腔注射小剂量链脲佐菌素(STZ)以建立2型糖尿病大鼠模型。建模成功后,连续药物干预4周,观察大鼠血糖水平变化,运用反转录定量PCR(q RT-PCR)和免疫组化技术分别检测大鼠肠道组织SGLT1基因和蛋白的表达水平。结果与正常对照组比较,2型糖尿病模型对照组大鼠血糖明显升高78%,并显著上调肠道组织中SGLT1基因和蛋白的表达(P<0.05)。给药4周后,与模型对照组比较,拜唐苹干预组和格列美脲干预组明显降低糖尿病大鼠的血糖,拜唐苹干预组降低46%,格列美脲干预组降低24%,拜唐苹干预组和格列美脲干预组能够下调2型糖尿病大鼠肠道组织中SGLT1基因和蛋白的表达(P<0.05),在相同血糖水平下,拜唐苹干预组效果更显著。结论对SD大鼠给予高脂乳剂灌胃联合一次性小剂量STZ注射可以成功诱导2型糖尿病模型。拜唐苹和格列美脲对2型糖尿病大鼠有降低血糖的治疗作用,并且对糖尿病大鼠肠道SGLT1受体的表达有一定的影响。在相同血糖水平下,比较格列美脲和拜唐苹的干预效果显示,拜唐苹对2型糖尿病大鼠肠道SGLT1表达的影响更显著。

[Objective] To investigate the modeling method of rats with type 2 diabetes mellitus,compare the effect between acarbose（glucobay） and glimepiride on blood glucose level of rats with type 2 diabetes mellitus,and explore the influence of acarbose on expression of intestinal sodium-glucose co transporter 1（SGLT1） in rats with type 2 diabetes mellitus.[Methods]40 SD male rats were randomly divided into five groups： normal control group,normal control ＋ acarbose intervention group,type 2 diabetic model group,diabetic model ＋ acarbose intervention group,diabetic model ＋ glimepiride intervention group,8 rats in each group. The rats in the diabetic group were treated with the high fat emulsion gavage and high glucose drinking water. After 4 weeks of continuous intragastric administration,the rats in the model group were injected intraperitoneally with small dose of streptozotocin（STZ）to establish the model of type 2 diabetes mellitus. After successful modeling,the blood glucose levels of rats were observed for 4 weeks after continuous drug intervention. The expression levels of SGLT1 gene and protein in the intestinal tissues of rats were detected by q RT-PCR and immunohistochemistry techniques.[Results]Compared with the normal control group,the blood glucose of type 2 diabetes model group was increased by 78%,and the expression of SGLT1 gene and protein in intestinal tissue significantly increased（P0.05）. After 4 weeks of treatment,compared with model group,the blood glucose levels of diabetic rats in acarbose intervention group and glimepiride intervention group significantly reduced,which decreased by 46% and 24%respectively,and expressions of SGLT1 gene and protein in intestinal tissue of rats with type 2 diabetes mellitus in acarbose intervention group and glimepiride intervention group decreased（P 0.05）. At the same level of blood glucose,the acarbose intervention group showed more significant effect.[Conclusion]The type 2 diabetes model is successfully induced in SD rats by intragastric administration of high fat emulsion combined with single small dose injection of STZ. Acarbose and glimepiride have hypoglycemic effect in type 2 diabetic rats,and have a certain effect on the expression of intestinal SGLT1 receptor in diabetic rats. At the same level of blood glucose,acarbose has more significant effect on expression of intestinal SGLT1 in diabetic rats as compared with glimepiride.