目的研究阿魏酸在大鼠体内的绝对生物利用度(F_abs)及其吸收特点。方法建立人源结肠腺癌细胞系Caco-2单层细胞模型,LC-MS/MS法分析阿魏酸由绒毛面(AP侧)到基底面(BL侧)和由BL侧到AP侧两个方向的转运过程;用大鼠原位肠肝血管灌流模型研究阿魏酸在肠道的吸收率;通过测定大鼠ig和iv阿魏酸后的血药浓度计算其F_abs。结果阿魏酸的表观渗透系数(P_app)分别为P_{app AP→BL}:(10.24±1.58)×10 ^-6cm/s,P_appBL→AP :(11.25±1.45)×10^-6cm/s;在肠肝血管灌流模型中的吸收率为59.00%;在大鼠体内的F_abs为64.91%。结论 LC-MS/MS定量分析法灵敏、简单、专属性强;阿魏酸在Caco-2细胞具有良好的转运,在肠肝血管灌流模型中吸收速度快,主要吸收部位为小肠,阿魏酸ig给药后在大鼠体内达峰时间短,吸收、分布、消除较快。

ObjectiveTo study the absolute bioavailability (F_abs ) of ferulic acid in rats and its absorption properties. Methods Based on the LC-MS/MS method, Caco-2 (the human colon adenocarcinoma cell lines) cell monolayer model was applied to studying the absorption and transport of ferulic acid from apical (AP) to basolateral (BL) side and from BL to AP side; the in situ vascularly perfused intestine-liver preparation was used to investigate the intestinal absorption rate; the F_abs was calculated by measuring the plasma concentration after iv or ig administration of ferulic acid in rats. Results The apparent permeability coefficients of ferulic acid from AP to BL side (P_appAP→BL ) and from BL to AP side (P_{app BL→AP} ) were (10.24 ± 1.58) × 10 ^-6 and (11.25 ± 1.45) × 10^-6 cm/s,respectively; the intestinal absorption rate in the in situ vascularly perfused intestine-liver preparation was 59.00%; the F_abs was 64.91% in rats.Conclusion LC-MS/MS method is a simple, sensitive, and specific approach for the quantitative analysis; ferulic acid shows a good permeability in Caco-2 cells; a fast absorption in vascularly perfused intestine-liver preparation with the small intestine as a main absorptive site, and shortly reaches t max with rapid absorption, distribution, and elimination in rats in vivo after ig administration.

国家自然科学基金资助项目(81073141);广东省自然科学基金资助项目(9152402301000007)