[关键词]
[摘要]
该研究探讨了白簕中性多糖ATP1-1对2型糖尿病小鼠肠道二糖酶的调节作用。采用高脂饲料联合链脲佐菌素(STZ)诱导2型糖尿病小鼠模型,成模小鼠分为模型组、二甲双胍组[185 mg/(kg·d)]、ATP1-1高剂量组[80 mg/(kg·d)]及低剂量组[40 mg/(kg·d)],另设正常组。连续灌胃给药8周,期间测定小鼠空腹血糖值,葡萄糖、蔗糖及麦芽糖耐量,末次给药后测定体内、外二糖酶活性及蔗糖酶-异麦芽糖酶复合物(Sucrase-Isomaltase,SI)、胰高血糖素样肽-1(GLP-1)的mRNA表达。结果显示,ATP1-1高、低剂量组的血糖浓度较模型组分别下降27.06%、19.96%(p<0.01),葡萄糖、蔗糖、麦芽糖耐量明显改善(p<0.05)。体内实验表明,高剂量ATP1-1对十二指肠、空肠、回肠的蔗糖酶抑制率分别为48.29%、75.09%、31.41%;对麦芽糖酶抑制率分别为26.23%、18.34%、34.18%;体外实验可知,ATP1-1对十二指肠蔗糖酶、麦芽糖酶的半数抑制浓度IC50分别为3 381.00 μg/mL、226.50 μg/mL。同时,ATP1-1还可上调GLP-1 mRNA表达、下调SI mRNA表达(p<0.01)。因此,ATP1-1可抑制2型糖尿病小鼠肠二糖酶活性及表达,促进GLP-1表达改善2型糖尿病小鼠的高血糖状态。
[Key word]
[Abstract]
This study investigated the regulatory effect of neutral polysaccharide from Acanthopanax trifoliatus (L.) Merr (ATP1-1) on intestinal disaccharidase in type 2 diabetic mice. A Type 2 diabetic mouse model was established through the induction by high-fat diet combined with streptozotocin (STZ). All diabetic mice were divided into 4 groups: model group, metformin group [185 mg/(kg·d)], high-dose ATP1-1 group [80 mg/(kg·d)], and low-dose ATP1-1 group [40 mg/(kg·d)]. Normal group was also set separately. The mice were given continuous intragastric administration for 8 weeks, during which Fasting blood glucose (FBG), glucose, sucrose and maltose tolerance were determined. After the last administration, in vivo and in vitro disaccharidase activities as well as the mRNA expressions of sucrase-isomaltase (SI) and glucagon-like peptide-1 (GLP-1) were evaluated. The results showed that compared with the model group, the FBG of the mice in high-dose ATP1-1 and low-dose ATP1-1 groups decreased by 27.06% and 19.96%, respectively (p<0.01), and the glucose, sucrose and maltose tolerance of the diabetic mice were significantly improved (p<0.01). In vivo experiments showed that the inhibition rates of high-dose ATP1-1 on the sucrase of the duodenum, jejunum and ileum were 48.29%, 75.09% and 31.41%, respectively, with the inhibition rates against the corresponding maltases being 26.23%, 18.34%, and 34.18%, respectively. In vitro experimental results showed that the IC50 of ATP1-1 on the duodenal sucrase and maltase were 3 381.00 μg/mL and 226.50 μg/mL, respectively. Meanwhile, ATP1-1 could up-regulate GLP-1 mRNA expression and down-regulate SI mRNA expression (p<0.01). Therefore, ATP1-1 can inhibit the activity and expression of intestinal disaccharidase, and promote the expression of GLP-1 to improve the hyperglycemia state of type 2 diabetic mice.
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[基金项目]
广东省自然科学基金项目(2017A030313623);广东省大学生创新创业训练项目(S202110573028)