杠柳毒苷及其降解产物杠柳次苷在MDCK细胞的跨膜透过特性研究.docVIP

  杠柳毒苷及其降解产物杠柳次苷在 MDCK 细胞的跨膜透过特性研究# 邓逢春，李超，何新** 5 10 （天津中医药大学中药学院，天津 300193） 摘要：目的：应用 MDCK 细胞模型研究和比较杠柳毒苷及其降解产物杠柳次苷在的跨膜透 过特性。方法：采用 MDCK 细胞模型研究杠柳毒苷和杠柳次苷的跨膜过程。通过测定杠柳 毒苷和杠柳次苷在 MDCK 细胞模型的透过量及表观渗透系数（Papp），比较二者的跨膜透 过能力。结果：在 MDCK 细胞模型上,拉贝洛尔和醋丁洛尔的 Papp 分别为(10.6 ± 0.12)× 10-6cm/s 和（1.27 ± 0.04）×10-6cm/s；杠柳毒苷和杠柳次苷 Papp 分别为（0.58 ± 0.27） ×10-6cm/s 和（22.8 ± 4.78）×10-6cm/s，杠柳次苷的 Papp 约为杠柳毒苷的 39 倍。结论： 杠柳毒苷降解一个糖基后，其代谢产物杠柳次苷在 MDCK 细胞的跨膜透过能力显著提高。 关键词：杠柳毒苷；杠柳次苷；MDCK 细胞模型 中图分类号：R969.1 15 Permeability study of periplocin and its metabolites periplocymarin by MDCK cell model Dengfengchun, Lichao, Hexin (Faculty of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,312 20  Abstract: Anshanxi Road, Nankai District,Tianjin 300193, P.R. China.) Objective: To study and compare the permeability of periplocin and its metabolite periplocymarin through MDCK cell monolayer. Methods: Using MDCK cell monolayer as an intestinal epithelial cell model, transmembrane transports of periplocin and periplocymarin were studied from apical side (AP)to basolateral side (BL) The ability of transmembrane transport was 25 30 35 40 compared between the periplocin and periplocymarin by determining the amount of drug transported and the apparent permeability coefficient (Papp)in the MDCK cell model. Results: The Papp values (from AP to BL) of labetalol and acebutolol were (10.6 ± 0.12)×10-6cm/s and (1.27 ± 0.04)×10-6cm/s, separately; The Papp values (from AP to BL) of periplocin and its metabolite periplocymarin were (0.58 ± 0.27)×10-6cm/s and (22.8 ± 4.78)×10-6cm/s respectively. The Papp value of periplocymarin was about thirty nine times higher than that of periplocin. Conclusion: After deglycosylation, the permeability of the metabolite, periplocymarin is better than that of periplocin. Key words: Periplocin; Periplocymarin; MDCK cell model 0 引言 杠柳毒苷是中药香加皮中的主要效应成分，其结构式为杠柳苷元-D-（加拿大麻糖）-D- （葡萄糖）。药理研究表明，杠柳毒苷具有强心[ 1,2]和抗肿瘤作用[3, 4,5]。药物代谢动力学研 究表明，杠柳毒苷是消除快而且口服生物利用度很低的药物[6]；杠柳毒苷主要经胆汁原型排