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异丹叶大黄素具有抗炎、抗氧化、抗癌等药理活性。该文研究了异丹叶大黄素在Caco-2细胞模型上的吸收转运机制。采用UPLC法,应用PDA检测器在310 nm处对异丹叶大黄素进行含量测定并计算表观渗透系数P_(app)。考察不同浓度异丹叶大黄素在Caco-2细胞上的毒性以确定转运实验的给药浓度。探讨了时间、浓度、温度、转运体抑制剂对异丹叶大黄素在体外细胞模型上跨膜转运的影响。实验结果表明,异丹叶大黄素在10~60μmol·L~(-1),孵育14 h内,对Caco-2细胞没有明显毒性。异丹叶大黄素在Caco-2细胞模型上的转运具有一定的浓度依赖性,其表观渗透系数P_(app)大于10×10~(-6)cm·s~(-1),易被Caco-2细胞吸收。BL侧的转运量在3 h达到最大值,6 h有所下降。4℃条件下,P_((app)(AP-BL))与P_((app)(BL-AP))均比37℃条件显著减小。加入P-gp转运体抑制剂维拉帕米后P_((app)(AP-BL))明显增大;加入MRP转运体抑制剂丙磺舒和MK-571后,P_((app)(BL-AP))明显减小。研究结果提示,异丹叶大黄素在Caco-2细胞模型上的转运方式主要是被动扩散,P-gp及MRP可能参与了异丹叶大黄素的外排转运。
Isoflavones emodin has anti-inflammatory, anti-oxidation, anti-cancer and other pharmacological activities. In this paper, the absorption and transport mechanism of isoflavone in Caco-2 cell model was studied. Using UPLC method, PDA detector was used to determine the content of emodin emodin at 310 nm, and the apparent permeability coefficient P app was calculated. To investigate the toxicity of different concentrations of isoflavones on Caco-2 cells to determine the concentration of drug delivery in the transport experiment. The effects of time, concentration, temperature, and transporter inhibitor on the transmembrane transport of iso-eudragango in vitro were explored. The experimental results showed that isoflavone emodin had no obvious toxicity on Caco-2 cells within 10-60 μmol·L -1 for 14 h. The transport of isoflavones in Caco-2 cells was dependent on the concentration, and the apparent permeability coefficient P app was more than 10 × 10 -6 cm · s -1. Caco-2 cells absorb. The amount of transport on the BL side reached its maximum at 3 h and decreased at 6 h. Under 4 ℃, P_ ((AP-BL)) and P_ (APP) (BL-AP) decreased significantly at 37 ℃. After the addition of P-gp transporter inhibitor verapamil, P (AP-BL) was significantly increased. After adding MRP transporter probenecid and MK-571, -AP)) was significantly reduced. The results suggest that the isodense emodin transport in the Caco-2 cell model is mainly passive diffusion, P-gp and MRP may be involved in the efflux transport of isoflavones emodin.