基于Caco-2细胞单层模型对盐酸氨溴索吸收机制的研究  

Absorption mechanism of ambroxol hydrochloride in the Caco-2 cell monolayer model

作　　者：梁秋玲 朱叶萌[1] 麦子盈 王凤姬 龙淑娴 王弋[1] 饶子亮[1] 邝少松[1] LIANG Qiuling;ZHU Yemeng;MAI Ziying;WANG Fengji;LONG Shuxian;WANG Yi;RAO Ziliang;KUANG Shaosong(Guangdong Medical Laboratory Animal Center,Foshan 528248,China)

机构地区：[1]广东省医学实验动物中心,广东佛山528248

出　　处：《中国比较医学杂志》2020年第6期47-53,共7页Chinese Journal of Comparative Medicine

基　　金：广东省省级科技计划项目(2019A030317015)。

摘　　要：目的通过Caco-2细胞单层模型研究盐酸氨溴索(ambroxol hydrochloride,AMB)的吸收机制,提高其生物利用度。方法通过跨上皮电阻(transepithelial electrical resistancev,TEER)、低渗透性药物阿昔洛韦的表观渗透系数Papp(AP→BL)和罗丹明123的外排率(efflux ratio,ER)验证Caco-2细胞单层模型的完整性和功能性。考察浓度、药物相互作用、体液p H对AMB的Papp(AP→BL)和ER值的影响。结果整个实验过程中Caco-2细胞单层的TEER>200Ω·cm^2,阿昔洛韦的Papp(AP→BL)<10^-6cm/s,罗丹明123的ER>2。与高渗透性对照组比较,AMB低剂量组的Papp(AP→BL)显著降低(P<0. 01),ER值无显著差异(P> 0. 05)。与AMB单独给药组比较,联合给药组的AMB Papp(AP→BL)值显著降低(P <0. 05),ER值无显著差异(P> 0. 05)。与AMB低p H组比较,AMB中、高p H组的Papp(AP→BL)显著增高(P<0. 01)。结论 AMB为易化扩散转运方式,与METO联合给药不利于AMB的吸收,提高肠液p H可促进AMB的吸收。Objective To study the absorption mechanism and improve the bioavailability of ambroxol hydrochloride(AMB)across the Caco-2 cell monolayer model.Methods The integrity and functionality of the Caco-2 cell monolayer model were analyzed by the transepithelial electrical resistance(TEER),the apparent permeability coefficient(Papp)of acyclovir and the efflux ratio(ER)of rhodamine 123.The effects of drug concentration,drug-drug interaction and pH on the Papp(AP→BL)and ER of AMB were investigated using the Caco-2 cell monolayer model.Results The TEER values of all the permeation experiments were above 200Ω·cm^2.The Papp(AP→BL)of acyclovir was less than 1×10^-6 cm/s.Furthermore,the ER of rhodamine 123 was lower than 2,indicating that the Caco-2 monolayer model was successfully established in this experiment.Compared with the high permeability control group,the Papp(AP→BL)was significantly decreased in the low-dose AMB group,but the ER was not affected.There was also no difference in the ER between AMB used alone and in combination with METO;however,there was a significant increase in the Papp(AP→BL)in the monotreatment group.Furthermore,the Papp(AP→BL)of AMB transport under pH 6.5 showed a significant difference compared with that under pH 7.4 and 8.0(P<0.01).Conclusions The transport of AMB across the Caco-2 cell monolayer model was facilitated by diffusion,and combination therapy was not conducive to AMB absorption.However,an alkaline environment accelerated AMB absorption.

关 键 词：盐酸氨溴索 吸收机制 药物相互作用 PH CACO-2细胞单层模型 

分 类 号：R-33[医药卫生]