WX-JT复方降血糖作用研究

目的: 研究WX-JT复方对α-葡萄糖苷酶抑制作用,评价WX-JT复方长期给药对II型糖尿病KK-A^y小鼠血糖相关指标影响。 方法: ①体外反转肠囊试验:采用大鼠小肠制备反转肠囊作为α-葡萄糖苷酶的来源,采用经α-淀粉酶消化后的淀粉溶液作为底物,与不同浓度阿卡波糖及WX-JT复方于37 ℃反应2 h,通过最终葡萄糖产生量计算受试药的α-葡萄糖苷酶抑制率。②正常小鼠淀粉耐量试验:正常ICR小鼠禁食20 h后单次ig给予3 g·kg^-1淀粉溶液及45.24,90.48,180.96 mg·kg^-1 WX-JT复方,测定给予淀粉0,30,60,120 min后血糖,评价药物对血糖升高的抑制作用。③长期给药对II型糖尿病小鼠血糖的影响:采用自发II型糖尿病模型KK-A^y小鼠,分为模型对照组、阿卡波糖组、WX-JT复方低剂量组(180.96 mg·kg^-1)和高剂量组(361.92 mg·kg^-1),正常对照组采用C57 BL/6J小鼠。连续ig给药9周,定期测定空腹血糖和非空腹血糖值;试验结束前进行口服葡萄糖耐量试验(OGTT)和糖基化血红蛋白(HbA1c)测定。 结果: 7~189 mg·L^-1WX-JT复方体外能浓度依赖地抑制α-葡萄糖苷酶活性,抑制率为16.6%~86%;90.48,180.96 mg·kg^-1 WX-JT复方明显降低正常小鼠淀粉耐量试验餐后30,60 min血糖;180.96,361.92 mg·kg^-1 WX-JT复方长期给药显著降低自发II型糖尿病模型KK-A^y小鼠空腹血糖、非空腹血糖和糖化血红蛋白水平,改善口服葡萄糖耐量,并呈明显量效关系。 结论: WX-JT复方具有明确的α-葡萄糖苷酶抑制作用,长期给药明显改善KK-A^y小鼠血糖相关指标,表明WX-JT复方通过抑制α-葡萄糖苷酶活性而发挥降血糖作用。

Study on the Hypoglycemic Effect of WX-JT Compound

Objective:To evaluate the inhibitory activity of WX-JT on alpha glucosidase and the effects of WX-JT(a compound Chinese medicine) on indexes associated with blood glucose in type 2 diabetic KK-Ay mice.Method: ①Everted rat intestine experiment: normal adult Wistar rats were sacrificed and whole small intestine was removed and made into intestinal sac.The intestinal sac was placed inside the conical flask with stopper containing substrate with WX-JT and acarbose.After incubating at 37 ℃ for 2 h,liquid in all conical flask was collected and the glucose level was measured.②In vivo evaluation of oral starch tolerance experiment.Forty ICR mice were randomly divided into 5 groups,the fasting blood glucose was measured after all mice were fasted for 12 h.Mice in WX-JT group and acarbose group were given starch solution after acute treatment at 45.24,90.48,180.96 mg·kg-1WX-JT and acarbose respectively,and mice in control group were given starch solution in the same volume by gavage.The blood glucose was measured respectively at 30,60,120 min after oral administration.③All mice were divided into untreated group,acarbose group,WX-JT low(180.96 mg·kg-1) and high dose(361.92 mg·kg-1) treatment group according to FBG and weight.Ten C57 BL/6J mice were taken as normal group.Acarbose and WX-JT were given by oral administration for 9 weeks.Mice in normal group and untreated group were administered orally with sterile water in the same dosage.Fasting blood glucose was detected in every odd week and non-fasting blood glucose was detected in each even week.Oral glucose tolerance(OGTT) was detected 9 weeks later.The level of glycohemoglobin(HbA1c) was measured after all the mice were sacrificed.Result: ①The everted rat intestine experiment showed that 7-189 mg·L-1 WX-JT could inhibit the activity of alpha glucosidase enzyme in vitro in concentration-dependent manner and the inhibition rate was 16.6%-86%.②Oral starch tolerance experiment indicated that WX-JT could decrease the postprandial blood glucose in mice at 30 min and 60 min after oral administration,which revealed that 90.48,180.96 mg·kg-1 WX-JT could inhibit the activity of α-glucosidase enzyme in vivo.③At 3 and 9 weeks after treatment with 180.96,361.92 mg·kg-1 WX-JT,the fasting blood glucose,non-fasting blood glucose and the level of HbA1c in KK-Aymice decreased remarkably in dose-dependent manner.Oral glucose tolerance test revealed that WX-JT could improve the glucose tolerance of KK-Ay mice.Conclusion: Both in vivo and in vitro experiment indicate that WX-JT can inhibit the activity of α-glucosidase enzyme.After a long-term administration with WX-JT,the indexes associated with blood glucose in type 2 diabetic KK-Ay mice decreased significantly,which indicates that WX-JT can decrease blood glucose by inhibiting the activity of α-glucosidase enzyme.