目的从胰岛素依赖、α-葡萄糖苷酶抑制、胰岛素增敏3个方面考察山茱萸总萜(TCF)的降血糖作用途径。方法尾静脉注射链脲佐菌素(streptozocin,STZ,50 mg·kg^-1)建立SD大鼠胰岛素缺乏糖尿病模型,分为正常组、模型组、二甲双胍组0.1 g·kg^-1、参芪降糖颗粒组1.0 g·kg^-1及TCF高、中、低3个剂量组(0.10、0.05、0.025 g·kg^-1)灌胃(ig)给药4周。每周测其体重及血糖,4周后采血测糖化血红蛋白(Hb A1c)、糖化血清蛋白(GSP);选择正常ICR小鼠,分为正常组、二甲双胍组0.2 g·kg^-1、拜糖苹组0.1 g·kg^-1、参芪降糖颗粒组1.5 g·kg^-1、TCF高、中、低3个剂量组(0.20、0.10、0.05 g·kg^-1)。给药10 d后进行腹腔注射葡萄糖(2.5 g·kg^-1)或灌胃淀粉(3.0 g·kg^-1)小鼠糖耐量实验;选择正常SD大鼠,分为正常组、罗格列酮组0.02 g·kg^-1、格列吡嗪组0.02 g·kg^-1、TCF高、中、低3个剂量组(0.10、0.05、0.025g·kg^-1),给药7 d后进行腹腔注射葡萄糖耐量实验(IPGTT),并测定各时间点胰岛素水平。结果(1)TCF高剂量组可明显降低STZ模型大鼠Hb A1c(P〈0.05)、GSP(P〈0.05)水平;(2)TCF对ICR小鼠的葡萄糖耐量和淀粉糖耐量也有明显改善(P〈0.05);(3)TCF高剂量组可明显降低1 h内血糖水平和血清胰岛素水平(P〈0.05)。结论 TCF在抑制葡萄糖体内吸收、促进葡萄糖利用等方面具有较明显的作用,可通过非胰岛素依赖途径发挥降糖作用,是否具有α-葡萄糖苷酶抑制、胰岛素增敏作用有待进一步验证。
Aim To investigate the hypoglycemic pathway of terpenes from Cornus officinalis(TCF) from three aspects of insulin dependence,α-glucosidase inhibition,insulin sensitizing.Methods Insulin-deficient diabetes mellitus(DM) model was induced by tail vein injection of streptozotocin(STZ) into SD rats at the dose of 50 mg · kg^-1body weight.Rats were randomly divided into seven groups:control group(CON),model group(Model),metformin group(Met) 0.1g·kg^-1,shenqi jiangtang granules(Shenqi) group 1.0 g · kg^-1,three dose groups of TCF:0.10,0.05,0.025 g·kg^-1.Body weight and blood glucose were measured every week.After four weeks,glycosylated hemoglobin(Hb A1c),glycosylated serum protein(GSP) were determined.Normal ICR mice were divided into seven groups:CON,Model,Met group 0.2g · kg^-1,acarbose group(Acar) 0.1 g ·kg^-1,Shenqi group 1.5g·kg^-1,three dose groups of TCF:0.20 g · kg^-1;0.10g·kg^-1;0.05 g·kg^-1.After 10 days of administration,intraperitoneal injections of glucose and gavage starch tolerance tests were employed.Normal SD rats were divided into six groups:CON,rosiglitazone group 0.02 g·kg^-1,glipizide group 0.02 g·kg^-1,three dose groups of TCF:0.10,0.05,0.025 g·kg^-1.After seven days of administration,intraperitoneal glucose tolerance test(IPGTT) was employed and levels of insulin was determined.Results(1) High dose of TCF significantly reduced the level of Hb A1c(P〈0.05),GSP(P〈0.05) on STZ model rats;(2) TCF significantly improved the glucose tolerance and gavage starch tolerance in ICR mice(P〈0.05);(3) High dose of TCF significantly reduced the blood glucose and serum insulin level.Conclusions TCF has obvious effects on inhibiting glucose absorb and promoting the use of glucose.It is able to exert hypoglycemic effect through non-insulin dependent pathway,whereas,whether it has the effects of α-glucosidase inhibition and insulin sensitization should be further validated.