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目的:评价β-环糊精(β-CD)或二甲基-β-环糊精与脱氧胆酸钠(SDC)联用对胰岛素的吸收促进作用。方法:通过胰岛素降血糖作用来反映其吸收效果;用扫描电镜观察单次给药后的鼻纤毛毒性;测定亮氨酰氨肽酶的活性。结果:0.75％ SDC/β-CD(1:2)联用时,鼻腔给予胰岛素产生的降血糖作用相对缓慢而持久,血糖最低值为初始的(72.6±2.1)％,血糖-时间曲线在1至4h内较平稳。虽然与0.75％ SDC组比较,两组的最低血糖水平有显著性差异,但血糖-时间曲线上面积AOC_(0-t)值无显著性差异(P>0.05)。扫描电镜结果显示大鼠鼻腔给药4h后粘膜纤毛无明显改变。0.01％ SDC促吸收能力很弱,但仍有纤毛毒性。SDC与β-环糊精或二甲基-β-环糊精联用后,亮氨酰氨肽酶的活性抑制率由89.2％下降至60％-70％。结论:β-环糊精与SDC联用后,降低了SDC的纤毛毒性,但仍保留了较强的胰岛素吸收促进作用。这种促进作用并不是由于SDC浓度的降低,而是与亮氨酰氨肽酶的活性被抑制有关。
AIM: To evaluate the effects of β-cyclodextrin (β-CD) or dimethyl-β-cyclodextrin combined with sodium deoxycholate (SDC) on insulin absorption. Methods: The hypoglycemic effect of insulin was used to reflect its absorption effect. The nasal cilia toxicity after a single administration was observed by scanning electron microscopy. The leucyl aminopeptidase activity was determined. Results: When combined with 0.75% SDC / β-CD (1: 2), the hypoglycemic effect of nasal administration of insulin was relatively slow and sustained, with the lowest blood glucose value of 72.6 ± 2.1% and the blood glucose-time curve of 1 to 2 4h more stable. Although there was a significant difference in the lowest blood glucose level between the two groups compared with the 0.75% SDC group, there was no significant difference in the AOC 0-t value in the blood glucose-time curve (P> 0.05). Scanning electron microscopy showed no significant changes in mucociliary cilia 4h after nasal administration. 0.01% SDC promote absorption capacity is very weak, but still ciliary toxicity. After the combination of SDC with β-cyclodextrin or dimethyl-β-cyclodextrin, the leucyl aminopeptidase activity inhibition decreased from 89.2% to 60% -70%. Conclusion: The combination of β-cyclodextrin and SDC reduced the ciliary toxicity of SDC, but still retained a strong insulin absorption promoting effect. This promotion is not due to a decrease in SDC concentration, but rather to leucyl aminopeptidase activity.