目的探讨苦瓜蛋白酶抑制剂对苦瓜降糖多肽口服降糖活性的保护作用。方法单次iv四氧嘧啶80mg/kg给药建立糖尿病小鼠模型。以降糖多肽(20、10、5 mg/kg)iv给药,于0.5、2、4、68、h尾静脉取血测定空腹血糖;测定在不同降糖多肽与蛋白酶抑制剂配伍剂量下,ig给药21 d后的空腹血糖值;以降糖作用显著的配伍比例,ig给药7、142、1 d和停止给药7 d后测定血糖。结果降糖多肽于iv给药4 h后,高、中、低3个剂量均表现出显著降血糖效应(P<0.05、0.01);降糖多肽与抑制剂(300+300)(、100+100)、(100+50)(、100+25)mg/kg 4个配伍剂量组ig给药21 d后表现出显著降血糖效应,且以后两个剂量组ig给药的降血糖作用为更佳,停药7 d后给药组血糖值与模型组无显著差异。结论苦瓜蛋白酶抑制剂在ig给药过程中能够使苦瓜降糖多肽免遭消化系统的蛋白水解酶破坏而起保护作用,维持其降血糖药效,该作用与两者间的配伍剂量有关。

Objective To study the protection of protease inhibitor of Momordica charantia on activity of hypoglycemic peptides from M.charantia by ig administration.Methods An experimental diabetic mouse model was successfully induced by once iv injection of alloxan at a dose of 80 mg/kg.Diabetic mice were administered with the hypoglycemic peptides(20,10,and 5 mg/kg) by iv injection and blood glucose level was tested at 0.5,2,4,6,and 8 h.Different ratios of hypoglycemic peptides and protease inhibitior were given to diabetic mice for 21 d and then the blood glucose level was determined.The blood glucose level in the drug administration group,which showed significant hypoglycemic effect after 21 d ig administration,at different time points of 7,14,and 21 d after ig administration and 7 d after administration withdraw,was measured.Results The hypoglycemic peptides showed significant hypoglycemic effect after 4 h iv injection(P0.05 and 0.01).Four mixtures of hypoglycemic peptides and inhibitors [(300+300),(100+100),(100+50),and(100+25) mg/kg] showed significant hypoglycemic effect after 21 d ig administration(P0.05 and 0.01),and the hypoglycemic effects of the last two groups are better.The blood glucose level had no statistical difference between the test group and the control group after 7 d administration withdraw. Conclusion The protease inhibitors of M.charantia could protect the activity of the hypoglycemic peptide during ig administration,which relates to the ratio of hypoglycemic peptide and inhibitors.

国家“十一五”科技攻关资助项目(2006BAI06A16);上海市科委资助项目(04DZ19818)