【摘要】 目的:利用Caco-2细胞单层模型研究胰岛素的吸收机制。方法:利用Caco-2细胞单层模型研究壳聚糖浓度、胰岛素初始浓度、合用壳聚糖与羟丙-β-环糊精(HP-β-CD)、转运方向等条件对表观渗透系数的影响,测定了合用壳聚糖与HP-β-CD对跨上皮细胞电阻(TEER)的影响。结果:当壳聚糖浓度增加时,胰岛素的渗透量也随之增加,其中0％,0．5％及1．0％壳聚糖三者间的渗透系数有显著差异(P<0．05),而1．0％及1．5％壳聚糖间的渗透系数没有差别(P>0．05);当胰岛素初始浓度增加时,胰岛素在单位时间内的累积渗透量也随之增加;5％HP-β-CD与1％壳聚糖共用时与单用1％壳聚糖相比,其渗透系数有所提高(P<0．05);顶端到底端方向上的渗透系数大于底端到顶端方向上的渗透系数(P<0．05);当1．0％壳聚糖与5％HP-β-CD合用时与单用1．0％壳聚糖相比,其跨上皮细胞电阻进一步降低(P<0．05)。结论:胰岛素是以被动扩散的方式通过细胞旁路进行转运的,在吸收促进剂5％HP-β-CD和1％壳聚糖联合作用下,药物经细胞旁路的转运量增加。更多还原

【Abstract】 Objective:To investigate insulin absorption mechanism using Caco-2 monolayer model. Methods: The effects of chitosan concentrations, insulin initial concentrations, combination of chitosan with HP-β-CD, and transport direction on the apparent permeability coefficient (Papp) as well as co-use of chitosan and HP-β-CD on transepithelial electrical resistance (TEER) were investigated using Caco-2 monolayer model. Results:The chitosan concentrations were positively proportion to the quantity of insulin transport. A significant difference of the effects of 0% , 0.5% and 1.0% chitosan was shown in the Papp values (P < 0. 05). No significant difference of the effects of 1. 0% and 1.5% chitosan was found in the Papp value (P > 0. 05). The escalation of insulin initial concentrations resulted in the transport of insulin across the monolayer up. The combination of 5% HP-β-CD with 1% chitosan increased the Papp value compared with the use of 1 % chitosan alone (P < 0. 05) . The Papp value of apical to ba-solateral side appeared higher than that of basolateral to apical side. The co-use of 5% HP-β-CD and 1% chitosan decreased the TEER level, compared to the use of 1 % chitosan alone (P <0.05) . Conclusion: The insulin was transported by passive diffusion via paracellular route. The co-use of 5% HP-β-CD and 1% chitosan increases the transport level of insulin.更多还原