荞麦壳黄酮提取物对2型糖尿病大鼠的血糖改善作用及机制

摘要

Objective:To evaluate the improvement of blood glucose levels in type 2 diabetic rats using buckwheat hull extracts (BHEs) rich in flavonoids and to explore its possible mechanisms.Methods:The inhibitory effect of BHEs on α-glucosidase and α-amylase activities was evaluated in vitro,and the type of enzyme inhibition was determined by Lineweaver-Burk (L-B) analysis.Type 2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of streptozotocin (STZ),and then the rats were randomly divided into control (without induction of diabetes mellitus,given distilled water),model group (given distilled water),positive control group (gavaged with mefformin hydrochloride at 100 mg/(kg·d)),and low-,medium-and high-dose BHEs groups (50,100 and 200 mg/(kg·d),respectively).The administration by gavage once a day last for 2g days.The body weight,fasting blood glucose (FBG),fasting serum insulin (FINS),fasting C-peptide and oral glucose tolerance test (OGTT) were determined during this period.Results:The inhibitory activity of BHEs on α-glucosidase-maltose system was dose dependent with a percentage inhibition of 41.12％ at a concentration of 1 mg/mL.The data of enzyme kinetics showed the inhibition was competitive.In the model group,body weight was reduced by 33.1％,FBG was increased up to (17.85 ± 2.25) mmol/L as well as the levels of FINS and C peptide were reduced to 24.80％ and 12.77％,respectively (P ＜ 0.05),when compared with the normal control group.Compared with the model group,the BHEs groups showed a significant improvement in body weight loss after 28 days of invention,FBG levels in the medium-and high-dose groups were decreased by 39.4％ and 48.2％,respectively,and the area under the curve (AUC) of OGTT was declined by 47.36％ and 59.47％,respectively (P ＜ 0.05).Compared with the model group,the middle-and high-dose groups improved the levels of FINS by 32.79％ and 34.44％ and C-peptide by 7.40％ and 13.08％,respectively (P ＜ 0.05).Conclusion:BHEs can improve blood glucose level in a dose-dependent manner in type 2 diabetes induced by STZ as α-glucosidase inhibitors,and simultaneously can repair islet β-cell function.%目的:研究荞麦壳黄酮提取物(buckwheat hull extracts,BHEs)对2型糖尿病大鼠血糖水平改善作用和机制.方法:体外实验中,测定了BHEs抑制α-葡萄糖苷酶和α-淀粉酶活性,并采用Lineweaver-Burk作图法确定其抑制反应的类型.体内实验中,高脂饮食与注射链脲佐菌素(streptozocin,STZ)复合诱导制备2型糖尿病大鼠模型,分为正常组(未诱导,蒸馏水),模型组(诱导,蒸馏水),阳性对照组(盐酸二甲双胍,100mg/ (kg·d))和BHEs低、中、高剂量组(50、100、200mg/ (kg·d),分别标记为LBHEs、MBHEs、HBHEs).灌胃给药,每天1次,连续干预28 d,观察大鼠体质量、空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting serum insulin,FINS)和C肽水平变化,并进行口服糖耐量实验(oral glucose tolerance test,OGTT).结果:BHEs在α-葡萄糖苷酶-麦芽糖体系中与其抑制活性成剂量依赖关系,当BHEs质量浓度为1 mg/mL时抑制率为41.12％,酶促动力学数据表明其为竞争型抑制.STZ诱导的2型糖尿病大鼠实验结果显示,与正常组相比,模型组大鼠体质量减少了33.1％,FBG升高到(17.85±2.25) mmol/L,而FINS、C肽水平分别降低了24.80％和12.77％(P＜0.05);与模型组相比,BHEs实验组改善糖尿病大鼠体质量减少,且干预28 d后MBHEs组和HBHEs组大鼠FBG与干预前比较分别降低了39.4％和48.2％(P＜0.05),OGTT曲线下面积降低了47.36％、59.47％(P＜0.05),MBHEs组和HBHEs组同时改善大鼠血清FINS和C肽水平,与模型组相比分别提高了32.79％、34.44％和7.40％、13.08％ (P＜0.05).结论:BHEs抑制α-葡萄糖苷酶活性和修复胰岛细胞功能的双重机制改善STZ诱导的2型糖尿病大鼠的血糖指标,并呈现一定的剂量-效应关系.