胰岛素纳米粒对大鼠实验性糖尿病的降血糖作用

Hypoglycemic effect of insulin-nanoparticles on diabetic rats

目的 制备氰基丙烯酸正丁酯胰岛素纳米粒 (insulinnanoparticles INP) ,研究其理化特性 ,观察 sc和 po给药对糖尿病大鼠的降血糖作用 .方法 用改良的乳液聚合法制备氰基丙烯酸正丁酯胰岛素纳米粒 ,用透射电子显微镜观察 INP的大小、形态 ,用高压液相色谱法 (HPL C)测定其包裹率 ,用 ip四氧嘧啶制备糖尿病大鼠模型 .血糖用快速血糖仪测定 .用 t检验和 χ2 检验进行统计学处理 .结果 用改良的乳液聚合法制得的 INP粒径为 (30± 0 .5 ) nm,包裹率为 95 % ,给糖尿病大鼠 sc30 U·kg- 1 ,INP组 1h开始起作用 ,4～ 6 h达峰值 ,血糖降低 98% ,作用持续 2 4h,而普通胰岛素组 1h达峰值 ,最大降血糖幅度为 5 5 % ,作用持续 4h. sc 2 0 U· kg- 1 ,INP组1h开始起作用 ,4～ 6 h达峰值 ,最大降血糖幅度为 74% ,作用持续 2 0 h,而鱼精蛋白锌胰岛素组 1h开始起作用 ,4～ 6 h达峰值 ,最大降血糖幅度为 41% ,作用也持续 2 0 h.给糖尿病大鼠 po INP 12 0 U· kg- 1 ,1d后空腹血糖开始下降 ,3d效果最佳 ,血糖降低 89% ,5～ 7d后恢复高血糖 ,而 po普通胰岛素组血糖无明显变化 ,2～ 4d的血糖两组比较相差显著 (P<0 .0 5 ) . 5 0 U· kg- 1 组及 10 0 U· kg- 1 组作用持续时间均为 5d,12 0 U· kg- 1 组的作用时间为 7d.

AIM To investigate the characteristics of insulin nanoparticles(INP) and their hypoglycemic effect on the alloxan induced diabetic rats. METHODS INP was prepared by improved emulsion polymerization methods. The entrapment efficiency was measured by HPLC. The diabetic rats were induced by ip alloxan. RESULTS INP thus prepared was (30±0.5)nm in diameter with an entrapment efficiency 95%. Subcutaneously administrated INP to alloxan induced diabetic rats at a dose of 30 U·kg -1 induced 98% decrease of blood glucose at 4~6 h. The effect lasted for 24 h. Whereas the regular insulin hypoglycemic effect lasted only for 2~3 h with the strongest hypoglycemic effect of 55% at 1 h. Subcutaneously administrated INP at a dose of 20 U·kg -1 to alloxan induced diabetic rats induced 74% decrease of blood glucose at 4~6 h and the effect lasted for 20 h. The protamine zine insulin effect lasted for the same time with the strongest hypoglycemic effect of 41% at 4~6 h. When a single dose of INP at 120 U·kg -1 was given intragastrically (orally) to the diabetic rats, the blood glucose began to drop on the first day, the strongest hypoglycemic effect (about 89% decrease of blood glucose ) being observed on the third day. The hypoglycemic effect was maintained for 4~5 d. After 5~7 d blood glucose returned to the control values. The regular insulin rendered no effect on blood glucose after intragastric adminstration( P <0.05 ). The dose dependency was observed in both hypoglycemic effect and maintaining time with different doses of oral INP. CONCLUSION INP can preserve the biological activities of insulin very well. When subcutaneously administered to alloxan induced diabetic rats, INP has a prolonged hypoglycemic effect. Oral administration of INP also exerts a dose dependent hypoglycemic effect on experimental diabetes. INP might be of potential oral use for insulin.