重组生物合成人高血糖素对家兔低血糖模型的药效试验

Effects of recombinant biosynthetic human glucagons on hypoglycaemia model rabbits

目的:建立家兔低血糖模型,通过静脉注射评价重组生物合成人高血糖素(GCN)及国外已上市药(GlucaGen?)的升糖作用,为进一步研究提供药效学基础[1]。方法:家兔禁食过夜,皮下注射不同剂量(0.23、0.45 U·kg-1)的门冬胰岛素进行低血糖模型筛选,确定造模方式后,静脉注射给予GCN及GlucaGen?,低剂量为0.02 mg·kg-1、高剂量为0.1 mg·kg-1,门冬胰岛素给药5、15、30、60、70、80、90、100、110、120、135、150、180、240 min检测所有动物的血糖。结果:在本试验条件下,家兔皮下注射门冬胰岛素(0.45 U·kg-1)后出现持续的低血糖症状,模型成立。分别给予高低剂量(0.1、0.02 mg·kg-1)的GCN及GlucaGen?可见明显的剂量-效应关系,且二者药效作用基本一致(P>0.05);结论:在本试验条件下,皮下注射0.45 U·kg-1门冬胰岛素可形成家兔低血糖模型,GCN对胰岛素诱导的家兔低血糖模型有治疗作用,其疗效与GlucaGen?无显著性差异。

Objectives:To establish rabbit hypoglycaemia model in order to supply pharmacodynamics basis for further research using the glycemic impacts of both the recombinant biosynthetic human glucagons(GCN)and the abroad listed drug(GlucaGen?).Methods:The rabbits were fasted overnight and hypoglycaemia model was filtered by different doses of subcutaneous injection of insulin aspart(0.23 U·kg-1 and 0.45 U·kg-1).When the methods for constructing model was determined,different doses of GCN and GlucaGen?(low dose:0.02 mg·kg-1;high dose:0.1 mg·kg-1)were given by a vein injection.The blood sugar was determined at 5,15,30,60,70,80,90,100,110,120,135,150,180,and 240 min post injection of insulin aspart.Results:Sustained hypoglycaemia was observed in the rabbis injected with 0.45 U·kg-1 of insulin aspart in our study and the rabbit hypoglycaemia model was established.Dose-effect relationships were found in the rabbits injected with low dose(0.1 mg·kg-1 and 0.02 mg·kg-1)of both GCN and GlucaGen?and the two drugs showed similar effects(P<0.05).Conclusions:The rabbit hypoglycaemia model could be established through subcutaneous injection with 0.45 U·kg-1 of insulin aspart.GCN has therapeutic effects on the insulin induced rabbits hypoglycaemia model,which is not significantly different to the effects of the abroad listed drug GlucaGen?.